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Chemotactic Factor (chemotactic + factor)
Selected AbstractsExploring the mast cell enigma: a personal reflection of what remains to be doneEXPERIMENTAL DERMATOLOGY, Issue 2 2008Beate M. Henz Abstract: Mast cells are traditionally viewed as effector cells of allergic reactions and parasitic diseases, but their importance in host defense against bacteria, in tissue remodelling, their bone marrow and stem cell origin and a central role of the stem cell factor (SCF) as mast cell growth and chemotactic factor has been worked out only in recent years. Despite this, major aspects about the nature of the cells and their role in disease remain unclear. This holds in particular for the identification of mast cell precursors and the role of growth factors that stimulate specific mast cell commitment from stem cells, such as nerve growth factor, neutrotrophin-3 and certain interleukins, alone and during interaction with SCF. Early data suggesting also an involvement of specific transcription factors need to be expanded in this process. Furthermore, although mast cell proliferative disease (mastocytosis) has been shown to be often associated with SCF receptor c-kit mutations, reasons for the development of this disease remain unclear. This holds also for mast cell release mechanisms in many types of mast cell-dependent urticaria. Exciting new insights are emerging regarding the role of mast cells in bacterial infections, in defense against tumors, in wound healing and in the interplay with the nervous system, with hormones, and in the neurohormonal network. The aim of this reflection is to delineate the many known and unknown aspects of mast cells, with a special focus on their development, and to discuss in detail two mast cell-related diseases, namely mastocytosis and urticaria. [source] Neopterin and interleukin-8 , prognosis in alcohol-induced cirrhosisLIVER INTERNATIONAL, Issue 6 2000Christian Homann Abstract:Background: Neutrophil cytotoxity and activated macrophages have been implicated in the pathogenesis of alcohol-induced liver disease. The aim of this study was to relate plasma levels of neopterin, a marker of activation of the cellular immune system, and IL-8, a neutrophil chemotactic factor, with severity of liver disease and prognosis in patients with alcohol-induced cirrhosis. Methods: Plasma concentrations of neopterin and IL-8 were assessed in 81 patients with alcohol-induced cirrhosis admitted to the Department of Medicine B, Bispebjerg Hospital, Copenhagen, Denmark, and in 16 healthy controls. After a median follow-up period of 5 years, mortality and death causes were registered. The patients were divided into groups according to the major contributing cause of death: infection, upper gastrointestinal bleeding or hepatic coma. Results: Neopterin and IL-8 levels were increased in the cirrhosis patients, but not significantly related to Child-Pugh classification. Five-year mortality was 67%. High neopterin levels (>upper quartile) were an independent predictor of death (p=0.01, Log rank and p<0.02, Cox). High IL-8 levels (>upper quartile) were of no significant prognostic value for overall mortality. Causes of death related mortality were as follows (Log rank): Neopterin; p=0.009, p=0.84 and p=0.94, and IL-8; p=0.36, p=0.002 and p=0.27, respectively, according to infection, bleeding and coma as causes of death. Conclusions: Neopterin and IL-8 plasma levels are raised in patients with alcohol-induced cirrhosis, and are predictive of mortality associated with infections and upper gastrointestinal bleeding, respectively. [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] Acute but not chronic macrophage recruitment in filarial infections in mice is dependent on C-C chemokine ligand 2PARASITE IMMUNOLOGY, Issue 8 2007M. RAMESH summary Macrophages play an important role in the formation of granulomas and the clearance of Brugia pahangi infections in mice. However, the factors responsible for the recruitment of these cells to the site of infection are not known. In this study we examined the role of the C-C chemokine ligand 2 (CCL2; also known as macrophage chemotactic factor , MCP1) in macrophage recruitment in intraperitoneal infections with B. pahangi. We observed that CCL2 was expressed by peritoneal exudate cells and was present in the sera of wild-type mice. Serum levels of CCL2 peaked twice during the immune response, once during the early, acute phase and again during the late, chronic phase. To further elucidate the role of this chemokine in the anti-filarial immune response, we compared CCL2 deficient (CCL2,/,) mice to wild-type mice. We observed that macrophage recruitment was impaired only during the acute phase in the former. While macrophage recruitment was unaffected during the chronic phase, increased accumulation of B and T lymphocytes was seen in these mice. We further report that larval clearance and the in vitro adhesion of PECs to larvae were unimpaired in these mice. [source] Molecular mechanism of monocyte predominant infiltration in chronic inflammation: Mediation by a novel monocyte chemotactic factor, S19 ribosomal protein dimerPATHOLOGY INTERNATIONAL, Issue 11 2000Tetsuro Yamamoto A novel monocyte chemotactic factor, a cross-linked homodimer of S19 ribosomal protein (RP S19) was initially isolated from a rheumatoid arthritis synovial lesion. The RP S19 dimer causes the monocyte specific chemotaxis in vitro and the monocyte predominant infiltration in vivo, via its agonistic and antagonistic effects on the C5a receptors of monocytes and polymorphonuclear leukocytes, respectively. The agonistic effect is attributed to the similarity of regional structures between RP S19 and C5a, the complement C5-derived leukocyte chemotactic factor, although overall homology of the amino acid sequence between these molecules is only 4%. The antagonistic effect depends upon the C-terminal portion of RP S19. The RP S19 dimer is produced and released by apoptotic cells, and this dimer recruits monocytes from the circulation to the apoptotic lesion. The infiltrated monocytes/macrophages engulf the apoptotic cells, translocate to regional lymph nodes via lymphatics and present the antigenic information of the apoptotic cells to the T cell repertoire. In this manner, the apoptotic cell clearance system connects to the acquired immune system. The innate and acquired immune mechanisms, mediated by the RP S19 dimer, participate in the pathology of inveterate chronic inflammation such as rheumatoid arthritis. [source] ABSTRACTS: 12 The complement component C1q: A novel angiogenic factor?AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 20082TH -6TH JUNE 2008 TOP SELECTED ABSTRACTS, 4TH EMBIC SUMMER SCHOOL, BARCELONA, SPAIN Aim:, Decidual endothelial cells are able to synthesize C1q and express surface-bound C1q under physiological conditions. Since decidua is a site of active angiogenesis, we sought to ascertain whether C1q could play a role in this process. Material and Methods:, To confirm our hypothesis we used different approaches such as permeability, cell migration and proliferation assay, besides wound healing and aortic ring assay. Results:, C1q acts as a permeabilizing factor inducing the FITC-BSA leakage through a monolayer of endothelial cells (ECs). Next, we found that C1q was able to promote motility of ECs in a wound healing assay, and to recruit ECs acting as a chemotactic factor, furthermore C1q was also found to have an additional effect on EC inducing cell proliferation. To confirm and extend these data, we used the rat aortic ring assay to evaluate the ex vivo effect of C1q. Conclusion:, Based on our findings, we propose that C1q exerts unexpected proangiogenic effects. [source] Rapid activation of Mac-1(CD11b/CD18) molecules on macrophages by a new chemotactic factor ,Gasserokine' produced by Lactobacillus gasseri JCM1131TANIMAL SCIENCE JOURNAL, Issue 5 2002Haruki KITAZAWA ABSTRACT The chemoattractant activity of a new chemotactic factor, ,Gasserokine' produced by Lactobacillus gasseri JCM1131T, has been proposed as a novel immunological function of probiotic lactic acid bacteria. The focus of the present study was to understand the mechanism of the chemotaxis induced by Gasserokine, using activation of an adhesion molecule, Mac-1 (CD11b/CD18) on macrophages. The macrophage chemotaxis to Gasserokine was abolished by preincubation of macrophages with the anti-Mac-1 mAb. Gasserokine induced rapid serine phosphorylation of CD18 molecules within 1 min of stimulation, but the effect was short-lived. Substantial tyrosine phosphorylation was observed in CD18-associated protein of macrophages stimulated by Gasserokine. The tyrosine phosphorylation was confirmed in macrophages stimulated with Gasserokine and also serine/threonine phosphorylation was detected on CD18 molecules by laser microscopy using a double immunostaining method. These results suggest that selective activation of intracellular signaling cascades, such as the mitogen-activated protein kinase pathway, are related to the macrophage chemotaxis induced by Gasserokine. [source] Neutrophils: key mediators of tumour angiogenesisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2009Simon Tazzyman Summary It is now well known that most malignant tumours contain a significant amount of leucocytic infiltrates the presence of which has, on many occasions, been linked to poor patient prognosis. These leucocyte populations are recruited to tumours by chemotactic factors released by either viable or necrotic tumour cells, or by cells within the tumour stroma. In recent times, most studies have analysed the role that tumour-associated macrophages (TAM) have on tumour progression. However, there is now increasing evidence to show that neutrophils also actively participate in this process. Whilst there are some data to suggest that neutrophil-derived factors can promote genetic mutations leading to tumourigenesis, or secrete factors that promote tumour cell proliferation; there is now substantial evidence to show that neutrophils, like TAM, significantly affect tumour angiogenesis. In this review, we discuss the likely mechanisms by which neutrophils are recruited into the tumour and then elaborate on how these cells may induce tumour vascularization by the secretion of powerful pro-angiogenic factors. We also discuss possible future chemotherapeutic strategies that are aimed at limiting tumour angiogenesis by inhibiting neutrophil recruitment. [source] Cytokine-regulated accumulation of eosinophils in inflammatory diseaseALLERGY, Issue 8 2004M. Lampinen The role of cytokines in the accumulation of eosinophil granulocytes in inflamed tissue has been studied extensively during recent years, and these molecules have been found to participate throughout the whole process of eosinophil recruitment. Haematopoietic cytokines such as IL-3, IL-5 and GM-CSF stimulate the proliferation and differentiation of eosinophils in the bone marrow, and the release of mature eosinophils from the bone marrow into the blood is probably promoted by IL-5. Priming of eosinophils in the blood following, for example, allergen challenge is performed mainly by IL-3, IL-5 and GM-CSF. An important step in the extravasation of eosinophils is their adhesion to the vascular endothelium. Adhesion molecules are upregulated by, e.g. IL-1, IL-4, TNF- , and IFN- , and the same cytokines may also increase the affinity of adhesion molecules both on eosinophils and endothelial cells. Finally, a number of cytokines have been shown to act as eosinophil chemotactic factors, attracting the cells to the inflammatory focus in the tissue. Some of the most important eosinophil chemoattractant cytokines are IL-5, IL-8, RANTES, eotaxin, eotaxin-2, eotaxin-3, MCP-3, MCP-4 and TNF- ,. Th2 cells, mast cells and epithelial cells are important sources of proinflammatory cytokines, but in recent years, the eosinophils have also been recognized as cytokine-producing and thereby immunoregulatory cells. The aim of this paper is to review the role of cytokines in the process of eosinophil recruitment in asthma, allergy and ulcerative colitis. [source] Osteopontin deficiency impairs wear debris,induced osteolysis via regulation of cytokine secretion from murine macrophagesARTHRITIS & RHEUMATISM, Issue 5 2010Sadanori Shimizu Objective To investigate the molecular mechanisms underlying particle-induced osteolysis, we focused on osteopontin (OPN), a cytokine and cell-attachment protein that is associated with macrophage chemoattractant and osteoclast activation. Methods We compared OPN protein levels in human periprosthetic osteolysis tissues with those in osteoarthritis (OA) synovial tissues. To investigate the functions of OPN during particle-induced osteolysis in vivo, titanium particles were implanted onto the calvaria of OPN-deficient mice and their wild-type (WT) littermates. Mice were killed on day 10 and evaluated immunohistologically. The effects of OPN deficiency on the secretion of inflammatory cytokines were examined using cultured bone marrow,derived macrophages (BMMs). BMMs from OPN-deficient and WT mice were cultured with titanium particles for 12 hours, and the concentrations of inflammatory cytokines in the conditioned media were measured by enzyme-linked immunosorbent assay. Results Expression of OPN protein was enhanced in human periprosthetic osteolysis tissues as compared with OA synovial tissues. In the particle-induced model of osteolysis of the calvaria, bone resorption was significantly suppressed by OPN deficiency via inhibition of osteoclastogenesis, whereas an inflammatory reaction was observed regardless of the genotype. Results of immunostaining indicated that OPN protein was highly expressed in the membrane and bone surface at the area of bone resorption in WT mice. When BMMs were exposed to titanium particles, the concentration of proinflammatory cytokines, such as tumor necrosis factor ,, interleukin-1, (IL-1,), IL-1,, and IL-6, as well as chemotactic factors, such as monocyte chemoattractant protein 1 and macrophage inflammatory protein 1,, in the conditioned medium were significantly reduced by OPN deficiency. Whereas phagocytic activity of BMMs was not attenuated by OPN deficiency, phagocytosis-mediated NF-,B activation was impaired in OPN-deficient BMMs. These data indicated that OPN was implicated in the development of particle-induced osteolysis via the orchestration of pro-/antiinflammatory cytokines secreted from macrophages. Conclusion OPN plays critical roles in wear debris,induced osteolysis, suggesting that OPN is a candidate therapeutic target for periprosthetic osteolysis. [source] Benzydamine inhibits monocyte migration and MAPK activation induced by chemotactic agonistsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2003Elena Riboldi The present study was aimed to investigate the effect of benzydamine, an anti-inflammatory drug devoid of activity on arachidonic acid metabolism, on monocyte chemotaxis and to define the possible biochemical correlates of activity. Benzydamine inhibited monocyte chemotaxis in response to three classes of chemoattractants: the prototypic CC-chemokine CCL2 (MCP-1), the microbial product fMLP and the complement cascade component C5a. The effect was dose-dependent with IC50's of 100, 50 and 45 ,M for MCP-1/CCL2, fMLP and C5a, respectively. At the dose of 100 ,M, the effect resulted in a 50±10% inhibition of MCP-1/CCL2-induced chemotaxis and 53±6 and 54±5% inhibitions of chemotaxis in response of fMLP and C5a, respectively (n=3). Receptor expression as well as calcium fluxes in response to chemoattractants were not affected by benzydamine. Benzydamine strongly inhibited chemoattractant-induced activation of the mitogen-activated protein kinase (MAPK) ERK1/2, and of its upstream activator kinase MEK1/2. ERK1/12 activation in response to chemoattractants was 89,98% inhibited by a 100 ,M concentration of benzydamine with an IC50 of 30 ,M. Under the same experimental conditions, pretreatment with 100 ,M benzydamine caused a 75,89% inhibition of p38 activation (IC50 25 ,M). These results indicate that the anti-inflammatory activity of benzydamine is exerted at multiple levels, including monocyte migration to chemotactic factors associated to a blockage of ERK and p38 MAPK pathways. British Journal of Pharmacology (2003) 140, 377,383. doi:10.1038/sj.bjp.0705428 [source] Leukotrienes and other mast cell mediators cause asthmatic airway obstructionCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2004S.-E. Dahlén Summary From an evolutionary perspective, bronchoconstriction is a highly conserved mechanism for defence against stimuli that are noxious for the lung and airways. The presence of mast cells in all layers of the airways makes them ideally situated to function as sensors of environmental changes that require such a host defence reaction. In addition to being activated by high affinity IgE receptors, many other trigger factors are known to activate signal transduction pathways leading to mast cell degranulation. This includes changes in the physical and chemical composition of the environment, exposure to endotoxin and other microbial factors acting on Toll-like receptors [1], intake of certain drugs and in particular virtually all nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects with the peculiar syndrome aspirin-intolerant asthma (AIA) [2]. Irrespective of the trigger, the consequence of mast cell activation is release of biologically active smooth muscle stimulating mediators as well as the secretion of cytokines, chemotactic factors and enzymes that are believed to trigger further cascades contributing to long-term tissue remodelling and chronic airway inflammation. [source] | ||||||||||||||||||||||