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Neutrophil Function (neutrophil + function)
Selected AbstractsOxidative Stress and Neutrophil Function in Cats with Chronic Renal FailureJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2010R.F. Keegan Background: Oxidative stress is an important component in the progression of chronic renal failure (CRF) and neutrophil function may be impaired by oxidative stress. Hypothesis: Cats with CRF have increased oxidative stress and decreased neutrophil function compared with control cats. Animals: Twenty cats with previously diagnosed renal failure were compared with 10 age-matched control cats. Methods: A biochemical profile, CBC, urinalysis, antioxidant capacity, superoxide dismutase (SOD) enzyme activity, reduced to oxidized glutathione ratio (GSH : GSSG), and neutrophil phagocytosis and oxidative burst were measured. Statistical comparisons (2-tailed t -test) were reported as mean ± standard deviation. Results: The CRF cats had significantly higher serum blood urea nitrogen, creatinine, and phosphorus concentrations than control cats, and significantly lower PCV and urine specific gravity than control cats. The GSH : GSSG ratio was significantly higher in the CRF group (177.6 ± 197, 61.7 ± 33; P < .02) whereas the antioxidant capacity was significantly less in the CRF group (0.56 ± 0.21, 0.81 ± 0.13 Trolox units; P < .005). SOD activity was the same in control and CRF cats. Neutrophil oxidative burst after Escherichia coli phagocytosis, measured as an increase in mean fluorescence intensity, was significantly higher in CRF cats than controls (732 ± 253, 524 ± 54; P < .05). Conclusions: The higher GSH : GSSG ratio and lower antioxidant capacity in CRF cats is consistent with activation of antioxidant defense mechanisms. It remains to be determined if supplementation with antioxidants such as SOD beyond the level of control cats would be of benefit in cats with CRF. [source] Patients with stable uncomplicated cirrhosis have normal neutrophil functionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2000Richard Kirsch Abstract Background: Neutrophil function has been reported to be abnormal in patients with cirrhosis. In order to evaluate the relative contribution of hepatocellular dysfunction and portalsystemic shunting of blood to these abnormalities, neutrophil function was studied in 18 patients with cirrhosis and portal hypertension. Nine patients, with extrahepatic portal hypertension (EPH) caused by portal vein thrombosis, who had no clinical, biochemical or histologic evidence of liver disease were also studied. Methods: Superoxide generation, phagocytosis, degranulation, leukotriene B4 release, candidacidal activity and quantitative and qualitative expression of the cell surface adhesive marker CD11b/CD18 were measured in these patients as well as in age- and gender-matched controls. Results: Patients with cirrhosis were found to have a small but statistically significant decrease in the expression of the CD18 component of MAC1 in N -formyl-methionyl-leucyl-phenylalanine-stimulated neutrophils (P = 0.04). No significant differences were found between either of the two patient groups and the control group for any of the other parameters of neutrophil function tested. Conclusions: These were unexpected findings in the light of data published elsewhere, which indicate impaired neutrophil function in patients with cirrhosis. The study suggests that patients with stable, uncomplicated cirrhosis and patients with EPH have normal neutrophil function. [source] Role of cytokines of the tumour necrosis factor family in the immune response to disseminated Candida albicans infectionBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000M. G. Netea Background Tumour necrosis factor (TNF) ,, lymphotoxin (LT) ,, CD40L and FasL are members of the TNF family that play a crucial role in modulation of the immune response. Their role in the defence against infection with Candida albicans was investigated in mice deficient in either TNF-, and LT-, (TNF,/, LT,/, mice), CD40L (CD40L,/, mice) or Fas (MRL/lpr mice). Methods Mortality rates were compared in mice infected intravenously with 106 colony-forming units of C. albicans per mouse. Results After infection with C. albicans the TNF,/, LT,/, mice had a significantly increased mortality rate compared with control mice (100 versus 40 per cent; P < 0·01). This was due to a 10,1000-fold increased outgrowth of the yeasts in the kidneys and liver of TNF,/, LT,/, mice (P < 0·01). Defective recruitment and phagocytosis, but not Candida killing, were responsible for these effects. CD40L,/, mice were also more susceptible to systemic candidiasis than the wild-type controls (mortality rate 80 versus 50 per cent; P < 0·05), and the growth of Candida in the kidneys was one order of magnitude higher in the deficient than in control mice (P < 0·05). Neutrophil function in the CD40L,/, mice was normal, whereas decreased Candida killing by macrophages through nitric oxide-dependent mechanisms was responsible for the effect of CD40/CD40L interactions. In contrast, Fas-defective MRL/lpr mice were significantly more resistant to disseminated candidiasis (mortality rate 50 versus 100 per cent; P < 0·01); this was mediated by the facilitation of neutrophil migration to the site of infection. Conclusion Cytokines of the TNF family play a crucial role in the modulation of host defence against fatal C. albicans infection. Their effects are exerted selectively at the level of neutrophil or macrophage function. © 2000 British Journal of Surgery Society Ltd [source] Abrogation of antibody-induced arthritis in mice by a self-activating viridin prodrug and association with impaired neutrophil and endothelial cell functionARTHRITIS & RHEUMATISM, Issue 8 2009Lars Stangenberg Objective To test a novel self-activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3-kinase inhibitor, in a model of antibody-mediated inflammatory arthritis. Methods The SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10-day disease course (serum-transfer arthritis). Protease activity was measured by a near-infrared imaging approach using a cleavable cathepsin,selective probe. Further near-infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil,endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay. Results SAV prevented ankle swelling in mice with serum-transfer arthritis in a dose-dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor , was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease-laden vesicles, were decreased by SAV administration. Conclusion A novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody-induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions. [source] Effect of byproducts from the ozonation of pyrene: Biphenyl-2,2,,6,6,-tetracarbaldehyde and biphenyl-2,2,,6,6,-tetracarboxylic acid on gap junction intercellular communication and neutrophil functionENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2005Stephanie L. Luster-Teasley Abstract In this study, biphenyl-2,2,,6,6,-tetracarbaldehyde, an initial by product formed from the ozonation of pyrene, and biphenyl-2,2,,6,6,-tetracarboxylic acid, a subsequent pyrene ozonation byproduct, were evaluated using two toxicology assays to compare the toxicity of ozonation byproducts with that of the parent compound. The first assay measured the potential for the compounds to block gap junctional intercellular communication (GJIC) using the scrape loading/dye transfer technique in normal WB-344 rat liver epithelial cells. The second assay evaluated the ability of the compounds to affect neutrophil function by measuring the production of superoxide in a human cell line (HL-60). Pyrene significantly blocked intercellular communication (f= 0.2,0.5) at 40 ,M and complete inhibition of communication (f < 0.2) occurred at 50 ,M. Gap junctional intercellular communication in cells exposed to biphenyl-2,2,,6,6,-tetracarbaldehyde reached f < 0.5 at a concentration of 15 ,M. At concentrations greater than 20 ,M, biphenyl-2,2,,6,6,-tetracarbaldehyde was cytotoxic and the inhibition of GJIC was caused by cell death. Biphenyl-2,2,,6,6,-tetracarboxylic acid was neither cytotoxic nor inhibitory to GJIC at the concentrations tested (10,500 ,M). Exposure to biphenyl-2,2,,6,6,-tetracarbaldehyde resulted in a concentration-dependent decrease in phorbol 12-myristate 13-acetate,stimulated O12 production. Neither exposure to pyrene nor biphenyl-2,2,,6,6,-tetracarboxylic acid caused a significant toxic effect on neutrophil function. [source] Effect of preoperative prophylaxis with filgrastim in cancer neck dissectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2000Wenisch Background Cancer surgery is known to lead to a deterioration in host defence mechanisms and an increase in susceptibility to infection after operation. Filgrastim enhances important antimicrobial functions of neutrophils including chemotaxis, phagocytosis and oxidative killing mechanisms. Methods The effects of additional (all patients received perioperative 3 , 25 mg kg,1 cefotiam and 1 , 20 mg kg,1 metronidazole) preoperative prophylaxis with filgrastim (5 ,g kg,1 12 h prior to surgery plus 5 ,g kg,1 0 h prior to surgery) on neutrophil phagocytosis and reactive oxygen radical production and postoperative infections in 24 patients undergoing cancer neck dissection were studied. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labelled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123, intracellularly. Results In the filgrastim-treated patients a higher neutrophil phagocytic capacity was seen intraoperatively, and 1,5 days postoperative, but not prior to surgery. Reactive oxygen radical production was significantly higher in filgrastim-treated patients prior to surgery, intraoperative and postoperative (1,5 days). 2/12 (17%) patients had postoperative infections in the filgrastim group and 9/12 (75%) patients had infections in the placebo group (P < 0.001). In particular, wound infections were recorded more often in the placebo group (1/12 vs. 6/12; P = 0.004). Conclusion We conclude that filgrastim enhances perioperative neutrophil function and could be useful in the prophylaxis of postoperative wound infections in patients undergoing cancer neck dissection. [source] Role for cAMP-protein kinase A signalling in augmented neutrophil adhesion and chemotaxis in sickle cell diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2007Andreia A. Canalli Abstract The significance of the leukocyte in sickle cell disease (SCD) pathophysiology is becoming increasingly recognised; we sought to examine whether the chemotactic properties of neutrophils of SCD individuals may be altered and, further, to better understand the signalling events that mediate altered SCD neutrophil function. Adhesion to immobilised fibronectin (FN) and chemotaxis of control and SCD neutrophils were assessed using in vitro static adhesion assays and 96-well chemotaxis chamber assays. Adhesion assays confirmed a significantly higher basal adhesion of SCD neutrophils to FN, compared with control neutrophils. Chemotaxis assays established, for the first time, that SCD neutrophils demonstrate greater spontaneous migration and, also, augmented migration in response to IL-8, when compared with control neutrophils. Co-incubation of SCD neutrophils with KT5720 (an inhibitor of PKA) abrogated increased basal SCD neutrophil adhesion, spontaneous chemotaxis and IL-8-stimulated chemotaxis. Stimulation of SCD neutrophils with IL-8 also significantly augmented SCD neutrophil adhesion to FN with a concomitant increase in cAMP levels and this increase in adhesion was abolished by KT5720. Interestingly, the adhesive properties of neutrophils from SCD individuals on hydroxyurea therapy were not significantly altered and results indicate that a reduction in intracellular cAMP may contribute to lower the adhesive properties of these cells. Data indicate that up-regulated cAMP signalling plays a significant role in the altered adhesive and migratory properties in SCD neutrophils. Such alterations may have important implications for the pathophysiology of the disease and the cAMP-PKA pathway may represent a therapeutic target for the abrogation of altered leukocyte function. [source] Role of osteopontin in neutrophil functionIMMUNOLOGY, Issue 4 2007Adeline Koh Summary Osteopontin (OPN) is important for the function of fibroblasts, macrophages and lymphocytes during inflammation and wound healing. In recent studies of experimental colitis we demonstrated exacerbated tissue destruction in OPN-null mice, associated with reduced tumour necrosis factor-, expression and increased myeloperoxidase activity. The objective of this investigation therefore was to determine the importance of OPN expression in neutrophil function. Although, in contrast to macrophages, neutrophils expressed low levels of OPN with little or no association with the CD44 receptor, intraperitoneal recruitment of neutrophils in OPN-null mice was impaired in response to sodium periodate. The importance of exogenous OPN for neutrophil recruitment was demonstrated by a robust increase in peritoneal infiltration of PMNs in response to injections of native or recombinant OPN. In vitro, OPN,/, neutrophils exhibited reduced chemokinesis and chemotaxis towards N -formyl methionyl leucyl phenylalanine (fMLP), reflecting a reduction in migration speed and polarization. Exogenous OPN, which was chemotactic for the neutrophils, rescued the defects in polarization and migration speed of the OPN,/, neutrophils. In contrast, the defensive and cytocidal activities of OPN,/, neutrophils, measured by assays for phagocytosis, generation of reactive oxygen species, cytokine production and matrix metalloproteinase-9, were not impaired. These studies demonstrate that, while exogenous OPN may be important for the recruitment and migration of neutrophils, expression of OPN by neutrophils is not required for their destructive capabilities. [source] Interferon-, activation of polymorphonuclear neutrophil functionIMMUNOLOGY, Issue 1 2004Terri N. Ellis Summary As current research illuminates the dynamic interplay between the innate and acquired immune responses, the interaction and communication between these two arms has yet to be fully investigated. Polymorphonuclear neutrophils (PMNs) and interferon-, (IFN-,) are known critical components of innate and acquired immunity, respectively. However, recent studies have demonstrated that these two components are not entirely isolated. Treatment of PMNs with IFN-, elicits a variety of responses depending on stimuli and environmental conditions. These responses include increased oxidative burst, differential gene expression, and induction of antigen presentation. Many of these functions have been overlooked in PMNs, which have long been classified as terminal phagocytic cells incapable of protein synthesis. As this review reports, the old definition of the PMN is in need of an update, as these cells have demonstrated their ability to mediate the transition between the innate and acquired immune responses. [source] Ageing and the neutrophil: no appetite for killing?IMMUNOLOGY, Issue 4 2000S. Butcher Summary In the armoury of the immune system developed to combat the various micro-organisms that could invade the host, the neutrophil forms the first line of defence against rapidly dividing bacteria and fungi. However, as humans age they become more susceptible to infection with these microbes and this has been ascribed to a decline in immune status, termed immune senescence. Here we summarize the literature specifically concerning the attenuation of neutrophil function with age and the possible mechanisms underlying their reduced response to infectious agents. [source] Patients with stable uncomplicated cirrhosis have normal neutrophil functionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2000Richard Kirsch Abstract Background: Neutrophil function has been reported to be abnormal in patients with cirrhosis. In order to evaluate the relative contribution of hepatocellular dysfunction and portalsystemic shunting of blood to these abnormalities, neutrophil function was studied in 18 patients with cirrhosis and portal hypertension. Nine patients, with extrahepatic portal hypertension (EPH) caused by portal vein thrombosis, who had no clinical, biochemical or histologic evidence of liver disease were also studied. Methods: Superoxide generation, phagocytosis, degranulation, leukotriene B4 release, candidacidal activity and quantitative and qualitative expression of the cell surface adhesive marker CD11b/CD18 were measured in these patients as well as in age- and gender-matched controls. Results: Patients with cirrhosis were found to have a small but statistically significant decrease in the expression of the CD18 component of MAC1 in N -formyl-methionyl-leucyl-phenylalanine-stimulated neutrophils (P = 0.04). No significant differences were found between either of the two patient groups and the control group for any of the other parameters of neutrophil function tested. Conclusions: These were unexpected findings in the light of data published elsewhere, which indicate impaired neutrophil function in patients with cirrhosis. The study suggests that patients with stable, uncomplicated cirrhosis and patients with EPH have normal neutrophil function. [source] Influence of aging on candidal growth and adhesion regulatory agents in salivaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 6 2001Toyohiro Tanida Abstract: Although oral candidiasis is frequently seen in the elderly, the factors determining candidal growth have insufficiently been explored. Hence, we examined the influence of aging on candidal adhesion and growth-inhibitory agents in saliva in 45 healthy volunteers and 60 patients with oral candidiasis. Both non-stimulated and stimulated salivary flow rates (SFRs) in the healthy controls decreased with aging. A gradual decrease of SFRs with aging was also observed in the patients, and the SFR levels were markedly lower than those in the controls. Although the salivary glucose levels were almost constant in all age groups, secretory immunoglobulin A and lactoferrin levels in saliva were significantly decreased statistically with age, and a marginal age-associated decrease in transferrin levels was also observed. In addition, the generation of superoxide from neutrophils in saliva and their Candida killing activity decreased with age, and these phenomena were more apparent in the patients. Furthermore, a larger number of Candida adhered to oral keratinocytes obtained from the elderly healthy controls than to those obtained from young controls. Correspondingly, keratinocytes from the aged controls showed more concanavalin-A binding sites than those from the young controls. However, oral Candida did not increase with increasing age in the controls, although an age-associated increase of oral Candida was observed in the patients. Taken together, these results indicate that the decreases of SFRs and salivary anti-candidal factors, suppression of salivary neutrophil function and the increase of candidal adhesion sites on keratinocytes predispose elderly individuals to oral candidiasis. [source] Acute Alcohol Intoxication During Hemorrhagic Shock: Impact on Host Defense From InfectionALCOHOLISM, Issue 4 2004K. L. Zambell Abstract: Background: Acute alcohol intoxication is a frequent underlying condition associated with traumatic injury. Our studies have demonstrated that acute alcohol intoxication significantly impairs the immediate hemodynamic, metabolic, and inflammatory responses to hemorrhagic shock. This study investigated whether acute alcohol intoxication during hemorrhagic shock would alter the outcome from an infectious challenge during the initial 24 hr recovery period. Methods: Chronically catheterized male Sprague Dawley® rats were randomized to acute alcohol intoxication (EtOH; 1.75 g/kg bolus followed by a constant 15 hr infusion at 250,300 mg/kg/hr) or isocaloric isovolemic dextrose infusion (dex; 3 ml + 0.375 ml/hr). EtOH and dex were assigned to either fixed-volume (50%) hemorrhagic shock followed by fluid resuscitation with Ringer's lactate (EtOH/hem, dex/hem) or sham hemorrhagic shock (EtOH/sham, dex/sham). Indexes of circulating neutrophil function (apoptosis, phagocytosis, oxidative burst) were obtained at baseline, at completion of hemorrhagic shock, and at the end of fluid resuscitation. Bacterial clearance, lung cytokine expression, and myeloperoxidase activity were determined at 6 and 18 hr after an intratracheal challenge with Klebsiella pneumoniae (107 colony-forming units). Results: Mean arterial blood pressure was significantly lower in acute alcohol intoxication-hemorrhagic shock animals throughout the hemorrhagic shock. In sham animals, acute alcohol intoxication alone did not produce significant changes in neutrophil apoptosis or phagocytic activity but significantly suppressed phorbol myristic acid (PMA)-stimulated oxidative burst. Hemorrhagic shock produced a modest increase in neutrophil apoptosis and suppression of neutrophil phagocytic capacity but significantly suppressed PMA-stimulated oxidative burst. Acute alcohol intoxication exacerbated the hemorrhagic shock-induced neutrophil apoptosis and the hemorrhagic shock-induced suppression of phagocytosis without further affecting PMA-stimulated oxidative burst. Fluid resuscitation did not restore neutrophil phagocytosis or oxidative burst. Acute alcohol intoxication decreased (,40%) 3-day survival from K. pneumoniae in hemorrhagic shock animals, impaired bacterial clearance during the first 18 hr postinfection, and prolonged lung proinflammatory cytokine expression. Conclusions: These results demonstrate that the early alterations in metabolic and inflammatory responses to hemorrhagic shock produced by acute alcohol intoxication are associated with neutrophil dysfunction and impaired host response to a secondary infectious challenge leading to increased morbidity and mortality. [source] Oxidative Stress and Neutrophil Function in Cats with Chronic Renal FailureJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2010R.F. Keegan Background: Oxidative stress is an important component in the progression of chronic renal failure (CRF) and neutrophil function may be impaired by oxidative stress. Hypothesis: Cats with CRF have increased oxidative stress and decreased neutrophil function compared with control cats. Animals: Twenty cats with previously diagnosed renal failure were compared with 10 age-matched control cats. Methods: A biochemical profile, CBC, urinalysis, antioxidant capacity, superoxide dismutase (SOD) enzyme activity, reduced to oxidized glutathione ratio (GSH : GSSG), and neutrophil phagocytosis and oxidative burst were measured. Statistical comparisons (2-tailed t -test) were reported as mean ± standard deviation. Results: The CRF cats had significantly higher serum blood urea nitrogen, creatinine, and phosphorus concentrations than control cats, and significantly lower PCV and urine specific gravity than control cats. The GSH : GSSG ratio was significantly higher in the CRF group (177.6 ± 197, 61.7 ± 33; P < .02) whereas the antioxidant capacity was significantly less in the CRF group (0.56 ± 0.21, 0.81 ± 0.13 Trolox units; P < .005). SOD activity was the same in control and CRF cats. Neutrophil oxidative burst after Escherichia coli phagocytosis, measured as an increase in mean fluorescence intensity, was significantly higher in CRF cats than controls (732 ± 253, 524 ± 54; P < .05). Conclusions: The higher GSH : GSSG ratio and lower antioxidant capacity in CRF cats is consistent with activation of antioxidant defense mechanisms. It remains to be determined if supplementation with antioxidants such as SOD beyond the level of control cats would be of benefit in cats with CRF. [source] Are individuals with lower neutrophil oxidative burst activity more prone to Helicobacter pylori infection?LUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 3 2008Masashi Matsuzaka Abstract Helicobacter pylori infection has been reported to cause enhanced reactive oxygen species in the gastric mucosa. We examined the relationship between H. pylori infection and neutrophil function of peripheral blood. The subjects were 904 volunteers who participated in the Iwaki Health Promotion Project in 2005. 158 subjects who were infected with H. pylori in 2005 also participated in this project in 2006 and were categorized into two groups: the eradication group, in which H. pylori was successfully eradicated during the 12 month period, and the non-eradication group, in which eradication was unsuccessful or the subjects did not receive eradication therapy. The laboratory assays performed were: a titre of H. pylori antibody; neutrophil counts; and oxidative burst activity (OBA) of neutrophils. Logistic regression analysis was executed, with H. pylori infection as the dependent variable and other items as the independent variables. OBA showed an inverse association with H. pylori infection in 2005. Additionally, when comparing the eradication and non-eradication groups, the change rates of OBA between 2005 and 2006 did not show any significant difference. It was concluded that H. pylori infection does not lower OBA, but those individuals in whom OBA was lower were more prone to H. pylori infection. Copyright © 2008 John Wiley & Sons, Ltd. [source] The main neutrophil and neutrophil-related functions may compensate for each other following exercise,a finding from training in university judoistsLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 1 2007Noriko Mochida Abstract In order to clarify the relationship between exercise and neutrophil function, we measured three major neutrophil and neutrophil-related functions, viz. the reactive oxygen species (ROS) production capability and phagocytic activity (PA) of neutrophils and serum opsonic activity (SOA), simultaneously before and after a unified loading exercise under three different sets of conditions. Thirteen female collegiate judoists were examined with a unified exercise loading (2 h) immediately before and after a 64 day training period. Immediately thereafter, the athletes took part in a 6 day intensified training camp, following which the same exercise loading was repeated. Responses from circulating neutrophils were estimated by comparing the two sets of values obtained before and after the two instances of exercise loading. The parameters assessed included neutrophil count, SOA, PA and ROS production capability. ROS production increased after the exercise loading performed immediately before and after the 64 day training period just before the camp, (p < 0.01) but decreased following the exercise loading performed after the camp (p < 0.05). This suggested depressed bacteriocidal capability of the circulating neutrophils. PA decreased after the exercise loading sessions imposed prior to and after the 64 day training period (p < 0.01) but did not change in the loading session after the camp. No changes were seen in SOA produced with the loading exercise either before the 64 day exercise period or before the camp, but increased significantly following the post-camp session (p < 0.05). In conclusion, athletic training-induced changes in immune functional activities of neutrophils, such as ROS production and PA, and neutrophil-related factors, such as SOA, may compensate for each other to maintain the overall integrity of the neutrophil immune function. Copyright © 2006 John Wiley & Sons, Ltd. [source] Effects of edaravone on human neutrophil functionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2005K. Mikawa Background:, Neutrophils play a crucial role in the antibacterial host defence system. Edaravone is used in critically ill patients who are often immuno-compromised secondary to concomitant disease or immunosuppressive therapy. The aim of the current study was to assess the effect of edaravone, a novel free-radical scavenger, on several aspects of human neutrophil function using an in vitro system. Methods:, Chemotaxis, phagocytosis, reactive oxygen species (ROS) production by neutrophil (cellular) and xanthine-xanthine oxidase (acellular) systems, and intracellular calcium ion levels ([Ca2 + ]i) were measured in the absence and in the presence (at a clinically relevant concentration, and 0.1-fold, and 10-fold this concentration) of edaravone. Results:, The clinically relevant concentration of edaravone did not inhibit chemotxais, phagocytosis, or superoxide production of neutrophils. Even at its ordinary clinical plasma concentration, the drug inhibited hydrogen peroxide (H2O2) and hydroxyl radical (OH·) generation in the cellular (neutrophil) as well as in the cell-free (xanthine-xanthine oxidase) system (P < 0.05). Edaravone did not affect elevation of [Ca2 + ]i in neutrophils stimulated by a chemotactic factor. Conclusions:, These findings suggest that edaravone quenched H2O2, and OH· generated rather than impaired the ability of neutrophils to produce the ROS. However, further studies using in vivo systems are required to elucidate the effects of edaravone on neutrophil function in clinical settings. [source] Bactericidal activity of neutrophils with reduced oxidative burst from adults with bronchiectasisAPMIS, Issue 2 2009PAUL KING Recent work has shown that the most common abnormality on screening of immune function in cohort of adult subjects with bronchiectasis was a low neutrophil oxidative burst. To assess the functional significance of a low oxidative burst in subjects with idiopathic bronchiectasis. Neutrophils with a low oxidative burst were obtained from six bronchiectasis patients and assessed for their ability to kill Staphylococcus aureus. The results were compared with those obtained using neutrophils from 12 healthy controls subjects and control neutrophils treated with dimethylthiourea (DMTU), an inhibitor of the oxidative burst. The results showed that the bronchiectasis subjects had significantly reduced killing of bacteria compared with controls (p<0.001). The addition of DMTU to neutrophils of control subjects significantly impaired both the oxidative burst and bactericidal activity. The addition of interferon-, enhanced oxidative burst in both groups. Abnormal neutrophil function in some subjects with bronchiectasis may account for their high rate of infection. [source] Neutrophil dysfunction in a family with a SAPHO syndrome,like phenotypeARTHRITIS & RHEUMATISM, Issue 10 2008Polly J. Ferguson SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is an inflammatory disorder of the bone, skin, and joints. We describe a family with multiple affected members who segregate a SAPHO syndrome,like phenotype, and we report the results of neutrophil studies and candidate gene analysis. We obtained written informed consent and a family history and reviewed medical records. We collected DNA and sequenced candidate genes, and we performed functional studies on neutrophils isolated from the proband and her mother. The pedigree segregated chronic osteomyelitis and cutaneous inflammation in a pattern that suggested an autosomal-dominant disorder. No coding sequence mutations were detected in PSTPIP1,PSTPIP2, LPIN2, SH3BP2, or NCF4. Analysis of neutrophil function in the proband, including nitroblue tetrazolium tests, myeloperoxidase assays, neutrophil chemotaxis, and neutrophil chemotaxis assays, revealed no identifiable abnormalities. However, an abnormality in the luminol, but not the isoluminol, respiratory burst assays following stimulation with phorbol myristate acetate (PMA) was detected in neutrophils isolated from the affected proband. Internal oxidant production was also reduced in the proband and her mother when neutrophils were treated with fMLP with or without platelet-activating factor, PMA alone, or tumor necrosis factor , alone. This family segregates a disorder characterized by chronic inflammation of the skin and bone. Functional differences in neutrophils exist between affected individuals and controls. The biologic significance of this defect remains unknown. Identification of the gene defect will help identify an immunologic pathway that, when dysregulated, causes inflammation of the skin and bone. [source] Blockade of parathyroid hormone,related protein prevents joint destruction and granuloma formation in streptococcal cell wall,induced arthritisARTHRITIS & RHEUMATISM, Issue 6 2003J. L. Funk Objective To determine whether parathyroid hormone,related protein (PTHrP), an interleukin-1,,inducible, bone-resorbing peptide that is produced in increasing amounts by the synovium in rheumatoid arthritis (RA), may play a role in the pathophysiology of joint destruction in RA. Methods PTHrP expression and the effect of PTHrP 1,34 neutralizing antibody on disease progression were tested in streptococcal cell wall (SCW),induced arthritis, an animal model of RA. Results As has been reported in RA, while serum levels of PTHrP did not change during SCW-induced arthritis, PTHrP expression dramatically increased in the arthritic synovium. Treatment with PTHrP neutralizing antibody (versus control antibody) did not affect joint swelling in SCW-treated animals. However, PTHrP antibody significantly inhibited SCW-induced joint destruction, as measured by its ability to block increases in serum pyridinoline (a marker of cartilage and bone destruction), erosion of articular cartilage, decreases in femoral bone mineral density, and increases in the numbers of osteoclasts in eroded bone. Unexpectedly, granuloma formation at sites of SCW deposition in the liver and spleen was also inhibited by PTHrP antibody, an effect associated with significant decreases in the tissue influx of PTH/PTHrP receptor,positive neutrophils and in SCW-induced neutrophilia. In vitro, neutrophil chemotaxis was stimulated by PTHrP 1,34. Conclusion These findings suggest that PTHrP, consistent with its previously described osteolytic effects in metastatic bone disease, can also be an important mediator of joint destruction in inflammatory bone disorders, such as RA. Moreover, this study reveals heretofore unknown effects of PTHrP peptides on neutrophil function that could have important implications in the pathogenesis of inflammatory granulomatous disorders. [source] Effects of heparin and related molecules upon neutrophil aggregation and elastase release in vitroBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Rachel A Brown Neutrophil-derived elastase is an enzyme implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Heparin inhibits the enzymatic activity of elastase and here we provide evidence for the first time that heparin can inhibit the release of elastase from human neutrophils. Unfractionated and low molecular weight heparins (UH and LMWH, 0.01,1000 U ml,1) and corresponding concentrations (0.06,6000 ,g ml,1) of nonanticoagulant O-desulphated heparin (ODH), dextran sulphate (DS) and nonsulphated poly- L -glutamic acid (PGA) were compared for their effects on both elastase release from and aggregation of neutrophils. UH, ODH and LMWH inhibited (P<0.05) the homotypic aggregation of neutrophils, in response to both N -formyl-methionyl-leucyl-phenylalanine (fMLP, 10,6M) and platelet-activating factor (PAF, 10,6M), as well as elastase release in response to these stimuli, in the absence and presence of the priming agent tumour necrosis factor-alpha (TNF- ,, 100 U ml,1). DS inhibited elastase release under all the conditions of cellular activation tested (P<0.05) but had no effect on aggregation. PGA lacked efficacy in either assay, suggesting general sulphation to be important in both effects of heparin on neutrophil function and specific patterns of sulphation to be required for inhibition of aggregation. Further investigation of the structural requirements for inhibition of elastase release confirmed the nonsulphated GAG hyaluronic acid and neutral dextran, respectively, to be without effect, whereas the IP3 receptor antagonist 2-aminoethoxydiphenylborate (2-APB) mimicked the effects of heparin, itself an established IP3 receptor antagonist, suggesting this to be a possible mechanism of action. British Journal of Pharmacology (2003) 139, 845,853. doi:10.1038/sj.bjp.0705291 [source] Evidence that glutamine is involved in neutrophil functionCELL BIOCHEMISTRY AND FUNCTION, Issue 2 2002Tania C. Pithon-Curi Abstract Phosphate-dependent glutaminase (PDG) activity, a key enzyme of glutamine metabolism, was determined in neutrophils obtained from the intra-peritoneal cavity (PC) or bronchoalveolar space (BAS) after administration of 1,ml or 100,,l, respectively of saline, glycogen solution (1%) or lipopolysaccharide (LPS 0.1,mg (100,,l),1). Neutrophils were obtained by lavage of both sites with 20,ml saline 24,h after the administration of the stimuli. Glycogen and LPS, depending on the site the cells were obtained from, differently modulated PDG activity. Cells from BAS stimulated by glycogen or LPS had raised PDG activity to 30.5,±,5.2 and 42.7,±,12.1,nmol,min,1,mg,1 protein, respectively, when compared with saline (9.1,±,0.9,nmol,min,1,mg,1 protein); mean,±,SEM. On the other hand, cells from PC showed different PDG activity: 52.0,±,12.6,nmol,min,1,mg,1 for saline, 36.5,±,9.5,nmol,min,1,mg,1 for glycogen, and 76.6,±,11.2,nmol,min,1,mg,1 for LPS; mean,±,SEM. Therefore, PDG activity varies with the site from which neutrophils are obtained and the stimulus imposed. The effect of glutamine on nitric oxide (NO) and tumour necrosis factor (TNF) production by peritoneal neutrophils, obtained after glycogen administration, cultured in the presence of LPS (0.5,,g,ml,1) was also examined. The addition of glutamine at concentrations varying from 2 to 20,mM did not markedly affect NO production. Glutamine alone at 2,mM did not modify the production of TNF but in the presence of LPS caused a significant decrease. So, glutamine may preserve the function of neutrophils during infections and injuries. Copyright © 2001 John Wiley & Sons, Ltd. [source] Assessing immune function in adult bronchiectasisCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006P. T. King Summary Bronchiectasis is characterized by chronic airway infection and damage and remains an important health problem. Recent literature has emphasized the role of host defence and immune deficiency in the pathogenesis of bronchiectasis, but there have been few studies of immune function in adult bronchiectasis. A comprehensive screen of immune function was conducted in 103 adult patients with bronchiectasis, encompassing full blood examinations, immunoglobulins and IgG isotypes, complement levels, lymphocyte subsets and neutrophil function. Full blood examinations were normal in this cohort, as were complement levels. Statistical analysis confirmed that a significant number of subjects had low levels of IgG3 (13 patients), B cell lymphocytes (six patients) and T helper cell lymphocytes (seven patients) when compared with controls (P < 0·05). The most common abnormality was found with testing of the neutrophil oxidative burst. All subjects had a normal neutrophil phagocytic function but 33 of the subjects had an oxidative burst that was below the normal range (P < 0001). Almost half the group (45 subjects) had abnormally low levels of one of these four parameters. The findings of low B cells, Th cells and oxidative burst in bronchiectasis are novel. The results emphasize the importance of immune function assessment for adult bronchiectasis. [source] Reduced post-operative neutrophil activation in liver transplant recipients suffering from post-hepatitic cirrhosisCLINICAL TRANSPLANTATION, Issue 6 2009Björn Jüttner Abstract:, Background:, It has been supposed that liver transplant recipients with hepatitis C virus infection have a higher incidence of infectious complications after transplantation. This study was designed to investigate whether neutrophil function is immediately affected by liver transplantation. Methods:, Biochemical values, plasma levels of myeloperoxidase (MPO), hydrogen peroxide production of neutrophils and neutrophil,platelet complexes were analyzed in 32 patients who underwent liver transplantation and 20 healthy volunteers. Results:, MPO levels were significantly increased 24 h after reperfusion. In post-hepatitic patients levels were significantly lower three d up to one wk post-transplant than in patients due to other liver diseases. One wk post-operatively the respiratory burst activity following N -formyl-methionyl-leucylphenylalanine (fMLP) or (tumor necrosis factor-,) TNF-,/fMLP stimulation was depressed in post-hepatitic recipients. Respiratory burst stimulated with phorbol 12-myristate 13-acetate in these patients was increased one wk after transplantation. One d after transplantation the neutrophil,platelet complexes decreased significantly throughout the post-operative period. Conclusions:, The results of this study suggest a reduced post-operative neutrophil activation in liver transplant recipients suffering from post-hepatitic cirrhosis compared to cirrhosis due to other causes. We hypothesized that neutrophil dysfunction in those patients depends on the underlying disease with an increased susceptibility to bacterial or fungal infections. [source] Agonists of proteinase-activated receptor-2 affect transendothelial migration and apoptosis of human neutrophilsEXPERIMENTAL DERMATOLOGY, Issue 10 2007Victoria M. Shpacovitch Abstract:, Skin is the first barrier preventing microorganism invasion in host. Wounds destroy this defense barrier and, without an appropriate care, may lead to sepsis. Neutrophil activation and immigration plays an important role at the inflammatory stage of wound healing. Neutrophils are known to express proteinase-activated receptors (PARs), which can be activated by serine proteases, also by enzymes involved in wound healing. We previously reported that PAR2 agonists up-regulate cell adhesion molecule expression and cytokine production by human neutrophils. Here, we demonstrate that PAR2 agonists (serine proteases as well as synthetic peptides) reduce transendothelial migration of neutrophils and prolong their life in vitro. Synthetic PAR2 agonist also enhanced protective interferon (IFN),-induced Fc,RI expression at neutrophil cell surface. Of note, IFN, is a cytokine, which was used in clinical trials to reactivate human neutrophil functions during sepsis. Moreover, we observed a significant increase of PAR2 expression on cell surface of neutrophils from septic patients as compared with healthy volunteers. Together, our results indicate that PAR2 may be involved in the pathophysiology of neutrophil-endothelial interactions during wound healing or later during sepsis in humans, potentially by affecting neutrophil apoptosis, transendothelial migration and Fc, receptor-mediated phagocytosis. [source] Signal transduction and functional changes in neutrophils with agingAGING CELL, Issue 4 2004Tamas Fulop Summary It is well known that the immune response decreases during aging, leading to a higher susceptibility to infections, cancers and autoimmune disorders. Most widely studied have been alterations in the adaptive immune response. Recently, the role of the innate immune response as a first-line defence against bacterial invasion and as a modulator of the adaptive immune response has become more widely recognized. One of the most important cell components of the innate response is neutrophils and it is therefore important to elucidate their function during aging. With aging there is an alteration of the receptor-driven functions of human neutrophils, such as superoxide anion production, chemotaxis and apoptosis. One of the alterations underlying these functional changes is a decrease in signalling elicited by specific receptors. Alterations were also found in the neutrophil membrane lipid rafts. These alterations in neutrophil functions and signal transduction that occur during aging might contribute to the significant increase in infections in old age. [source] A competitive marathon race decreases neutrophil functions in athletesLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 6 2003Daisuke Chinda Abstract A full marathon is the longest running race in official track events and is a form of acute exercise. However, no studies have examined the acute neutrophil function response to a competitive marathon race. Thirty-six male athletes who had just completed the 42.195 km course of the 50th Beppu-Oita Mainichi Marathon were enrolled in this study. Neutrophil oxidative burst activity, phagocytic activity and expression of CD11b and CD16 per cell were measured by flow cytometry immediately before and after the marathon. Total leukocyte/neutrophil counts increased significantly (p < 0.001), whereas total oxidative burst activity per neutrophil cell decreased significantly after the race (p < 0.001). Furthermore, total phagocytic activity per neutrophil cell also decreased after the race, although it was not significant (p = 0.08). Although CD11b expression per cell did not change, the expression of CD16 per cell significantly decreased (p < 0.001) after the race. In conclusion, a competitive marathon race decreased neutrophil functions (oxidative burst activity and phagocytic activity), which may be partly due to a decrease in CD16 expression. The increase in total neutrophil counts might reflect a compensatory response to counteract the decrease in neutrophil functions. Copyright © 2003 John Wiley & Sons, Ltd. [source] Immune effect of hypertonic saline: fact or fiction?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2004J. A. Kølsen-Petersen Hypertonicity affects many parts of the immune system. Animal studies and experiments in isolated cell cultures show that hypertonicity reversibly suppresses several neutrophil functions and at the same time up-regulates T-lymphocyte function. Infusion of hypertonic saline with or without colloids may thus, besides providing efficient plasma volume expansion, ameliorate the detrimental consequences on the immune function of trauma, shock, reperfusion, and major surgery. However, the few clinical studies conducted to date, specifically addressing the immune effect of hypertonic saline infusion, have shown little, if any, effect on markers of immune function, and larger clinical trials have not demonstrated benefit in terms of morbidity or mortality. Thus, as opposed to animal and cell-culture studies, the immune-modulating properties of hypertonic saline infusion would appear to be of limited value in clinical practice. This review presents in vitro studies, animal experiments, and clinical trials which investigated the consequences of hypertonic saline on markers of immune function. [source] Acute lymphoblastic leukemia in a patient with chronic granulomatous disease and a novel mutation in CYBB: First reportAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2005Baruch Wolach Abstract We report for the first time a child with chronic granulomatous disease (CGD) who developed acute lymphoblastic leukemia (ALL). The diagnosis of CGD was made at the age of 4 months, by studies of his neutrophil functions. The superoxide production of the cells was negligible, as was the bactericidal activity. He was found to have a deficiency of the gp91phox subunit of the leukocyte NADPH oxidase, with the X-linked inheritance of the disease. DNA analysis revealed a C nucleotide insertion between C1028 and T1029. This insertion has not been described before and causes a frameshift and a premature stop codon at amino-acid position 347. The mother was found to be a carrier of this mutation. At the age of 16 months, the patient developed T-cell ALL. He was treated for 2 years, and today, 10 years since the diagnosis, he is disease-free. During the course of ALL and later, he suffered from recurrent severe pyogenic infections, but careful detection of the etiological agent and promptly instituted specific treatment resulted in his complete recovery. Although primary immune deficiencies have been reported to have an increased tendency to develop malignancies, until now there have been no reports of CGD patients with ALL. Am. J. Hematol. 80:50,54, 2005. © 2005 Wiley-Liss, Inc. [source] Subproteome analysis of the neutrophil cytoskeletonPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2009Ping Xu Abstract Neutrophils play a key role in the early host-defense mechanisms due to their capacity to migrate into inflamed tissues and phagocytose microorganisms. The cytoskeleton has an essential role in these neutrophil functions, however, its composition is still poorly understood. We separately analyzed different cytoskeletal compartments: cytosolic skeleton, phagosome membrane skeleton, and plasma membrane skeleton. Using a proteomic approach, 138 nonredundant proteins were identified. Proteins not previously known to associate with the skeleton were: n -acetylglucosamine kinase, phosphoglycerate mutase 1, prohibitin, ficolin-1, phosphogluconate dehydrogenase, glucosidase, transketolase, major vault protein, valosin-containing protein, aldehyde dehydrogenase, and lung cancer-related protein-8 (LCRP8). The majority of these proteins can be classified as energy metabolism enzymes. Such a finding was interesting because neutrophil energy metabolism is unusual, mainly relying on glycolysis. The enrichment of phosphoglycerate mutase in cytosolic skeleton was additionally indicated by the use of Western blotting. This is the broadest subcellular investigation to date of the neutrophil cytoskeletal proteome and the first proteomic analysis in any cell type of the phagosome skeleton. The association of metabolic enzymes with cytoskeleton is suggestive of the importance of their localized enrichment and macromolecular organization in neutrophils. [source] | ||||||||||||||||||||||||||||