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Cellular Adhesion Molecules (cellular + adhesion_molecule)
Selected AbstractsCharacterization of the in vitro adherence behavior of ultrasound responsive double-shelled microspheres targeted to cellular adhesion moleculesCONTRAST MEDIA & MOLECULAR IMAGING, Issue 6 2006Susanne Ottoboni Abstract We have developed novel adhesion molecule-targeted double-shelled microspheres which encapsulate nitrogen. We report in vitro targeting studies utilizing these microspheres conjugated to target-specific antibodies directed towards ICAM-1 and VCAM-1. In static adherence experiments, the adherence patterns of microspheres conjugated to three different monoclonal antibodies (two targeted to ICAM-1 and one to VCAM-1) to their target surfaces were very different. Maximum microsphere adherence at the lowest target and/or ligand densities was observed with the VCAM-1 system. Differences in target-specific adherence were also observed between anti-ICAM-1 and anti-VCAM-1 microsphere conjugates in flow adherence studies. Equilibrium binding studies of the target proteins in solution to the microsphere-bound ligands showed that the affinity constants of two microsphere-bound monoclonal antibodies for their target proteins are similar. Thus, ligand,target affinity is not the only determinant of microsphere adherence to the target surface in our systems. Shear stress was found to have an effect on the mean diameter of adhered microspheres; a decrease in the mean diameter with increasing shear was observed. The magnitude of this effect was dependent on both microsphere-bound ligand and target surface densities, with a more pronounced change at lower densities. Adhered microspheres were readily detectable using ultrasound at the lowest tested surface density of 40,mm,2. Copyright © 2006 John Wiley & Sons, Ltd. [source] Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin testEXPERIMENTAL DERMATOLOGY, Issue 5 2003M. Caproni Abstract:, In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-,), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22,57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-, showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system. [source] Biliverdin therapy protects rat livers from ischemia and reperfusion injuryHEPATOLOGY, Issue 6 2004Constantino Fondevila Heme oxygenase (HO-1) provides a cellular defense mechanism during oxidative stress and catalyzes the rate-limiting step in heme metabolism that produces biliverdin (BV). The role of BV and its potential use in preventing ischemia/reperfusion injury (IRI) had never been studied. This study was designed to explore putative cytoprotective functions of BV during hepatic IRI in rat liver models of ex vivo perfusion and orthotopic liver transplantation (OLT) after prolonged periods of cold ischemia. In an ex vivo hepatic IRI model, adjunctive BV improved portal venous blood flow, increased bile production, and decreased hepatocellular damage. These findings were correlated with amelioration of histological features of IRI, as assessed by Suzuki's criteria. Following cold ischemia and syngeneic OLT, BV therapy extended animal survival from 50% in untreated controls to 90% to 100%. This effect correlated with improved liver function and preserved hepatic architecture. Additionally, BV adjuvant after OLT decreased endothelial expression of cellular adhesion molecules (P-selectin and intracellular adhesion molecule 1), and decreased the extent of infiltration by neutrophils and inflammatory macrophages. BV also inhibited expression of inducible nitric oxide synthase and proinflammatory cytokines (interleukin 1,, tumor necrosis factor ,, and interleukin 6) in OLTs. Finally, BV therapy promoted an increased expression of antiapoptotic molecules independently of HO-1 expression, consistent with BV being an important mediator through which HO-1 prevents cell death. In conclusion, this study documents and dissects potent cytoprotective effects of BV in well-established rat models of hepatic IRI. Our results provide the rationale for a novel therapeutic approach using BV to maximize the function and thus the availability of donor organs. (HEPATOLOGY 2004;40:1333,1341.) [source] Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapyJOURNAL OF INTERNAL MEDICINE, Issue 5 2002T. Apeland Abstract. Apeland T, Mansoor MA, Seljeflot I, Brønstad I, Gøransson L, Strandjord RE (Rogaland Central Hospital, Stavanger; and Ullevål University Hospital, Oslo; Norway). Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy. J Intern Med 2002; 252: 456,464. Objectives. Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. Design. Longitudinal and open intervention study. Setting. Two dialysis units in the County of Rogaland. Subjects. All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. Interventions. After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. Main outcome measures. Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins , markers of endothelial activation and (iii) serum malondialdehyde (S-MDA) , a marker of oxidative stress and lipid peroxidation. Results. The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). Conclusions. Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance. [source] Neopterin induces pro-atherothrombotic phenotype in human coronary endothelial cellsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2006P. CIRILLO Summary.,Background: Inflammation plays a pivotal role in atherothrombosis. Recent data indicate that serum levels of neopterin, a marker of inflammation and immune modulator secreted by monocytes/macrophages, are elevated in patients with acute coronary syndromes and seem to be a prognostic marker for major cardiovascular events. The aim of the present study was to determine whether neopterin might affect the thrombotic and atherosclerotic characteristics of human coronary artery endothelial cells (HCAECs). Methods and results: In HCAECs, neopterin induced TF-mRNA transcription as demonstrated by real time polymerase chain reaction and expression of functionally active tissue factor (TF) as demonstrated by procoagulant activity assay, and of cellular adhesion molecules (CAMs) as demonstrated by FACS analysis, in a dose-dependent fashion. These neopterin effects were prevented by lovastatin, a HMG-CoA reductase inhibitor. Neopterin-induced TF and CAMs expression was mediated by oxygen free radicals through the activation of the transcription factor, nuclear factor-kappa B (NF- ,B), as demonstrated by electrophoretic mobility shift assay and by suppression of CAMs and TF expression by superoxide dismutase and by NF- ,B inhibitor, pyrrolidine-dithio-carbamate ammonium. Conclusions: These data indicate that neopterin exerts direct effects on HCAECs by promoting CAMs and TF expression and support the hypothesis that neopterin, besides representing a marker of inflammation, might be an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. [source] Soluble cellular adhesion molecules, selectins, VEGF and endothelin-1 in patients with Wuchereria bancrofti infection and association with clinical statusPARASITE IMMUNOLOGY, Issue 1-2 2005P. Esterre SUMMARY Lymphatic filariasis, a mosquito-transmitted disease commonly known as Bancroftian filariasis, is characterized by debilitating pathology linked to the progression of lymphoedema to a chronic state of elephantiasis. We performed longitudinal measurements of endothelial adhesion and angiogenic molecules in 63 Polynesian patients living in an hyperendemic focus of Wuchereria bancrofti. Decreased serum concentrations of soluble (s-) L selectin (CD62L) were noticed in sera of of patients with chronic conditions (hydrocele and elephantiasis). Chyluria was associated with increased vascular endothelial growth factor (VEGF) levels, whereas elephantiasis presented a high endothelin-1 (ET-1) profile. By contrast, increased serum concentrations of soluble intercellular (sICAM-1, CD54), but not of vascular cell (sVCAM-1, CD106), adhesion molecules were observed in sera of patients with bacterial lymphangitis used as controls. These trends are consistent with the increased permeability of vascular structures, a major clinical feature observed in acute lymphatic pathology (of bacterial or filarial origin), and of fundamental differences in the pathogenesis of hydrocele and elephantiasis. Using markers correlated with the clinical status (high ET-1 and VEGF levels for elephantiasis and chyluria, respectively; low CD62L levels for hydrocoele and elephantiasis) it should be possible to monitor disease progression in lymphatic filariasis. [source] Expression of MAC-1 (CD11b) in acute myeloid leukemia (AML) is associated with an unfavorable prognosisAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2006Michaela Graf Abstract There is evidence to suggest, that cellular adhesion molecules and receptors could play a role in leukemia, e.g., through altered adhesive qualities of leukemic blasts. We have studied the expression of the ,2 -integrin Mac-1 (CD11b) on mononuclear cells in 48 patients with AML at first diagnosis by flow cytometry using a direct fluorescein-conjugated antibody. A case was defined as positive if more than 20% of the cells expressed Mac-1. Within the FAB types, we observed a high expression rate in cases with M5 (100% MAC-1+ cases, 73% MAC-1+ cells), M4 (75% MAC-1+ cases, 48% MAC-1+ cells) and in cases with FAB-M1 with 71% MAC-1+ cases and 29% MAC-1+ cells. Separating our patients' cohort in cytogenetic risk groups, we could detect significant higher proportions of MAC-1+, cases (88% vs. 27%, P = 0.005) and cells (51% vs. 16%, P = 0.015) with poor cytogenetic risk compared to the favorable risk group. For clinical evaluations only patients treated according to the protocols of the German AML Cooperative Group (AML-CG) were included (n = 29, cases with AML-M3 were excluded). More MAC-1+ cases and cells were found in the "non-responders" group (n = 8) compared to the "responders" group (n = 24). We can conclude that AML cases with high MAC-1 expression are characterized by a worse prognosis. Evaluation of MAC-1 expression in AML might therefore contribute clinically important data with respect to develop new therapies that influence the interactions between integrins like MAC-1 on leukemic cells and endothelial or immunoreactive cells. Am. J. Hematol. 81:227,235, 2006. © 2006 Wiley-Liss, Inc. [source] Inhibitory effect of pioglitazone on expression of adhesion molecules on neutrophils and endothelial cellsBIOFACTORS, Issue 1 2004Eiko Imamoto Abstract The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in various inflammatory and immune diseases. It has been suggested that peroxisome proliferator-activated receptor-, (PPAR-,, a member of the nuclear receptor superfamily of transcription factors) might be involved in the control of inflammation and in modulating the expression of various cytokines. The aim of this investigation was to evaluate the anti-inflammatory properties of PPAR-, activators, as well as the inhibitory effect of PPAR-, on the expression of adhesion molecules on leukocytes and vascular endothelial cells. Pioglitazone, a synthetic PPAR-, activator, suppressed the increase of CD11b/CD18 expression on FMLP-activated leukocytes, as detected by immunofluorescence flow cytometry. However, the FMLP-induced elevation of cytosolic Ca+2 in leukocytes was not suppressed by pioglitazone. Pioglitazone inhibited the expression of VCAM-1 protein and mRNA on activated human umbilical vein endothelial cells (HUVEC) after IL-1, stimulation, as detected by ELISA and real-time PCR. However, it showed little effect on the expression of ICAM-1 and E-selectin. The present study revealed that pioglitazone can influence monocyte-EC binding by inhibiting VCAM-1 expression on activated EC and neutrophil-EC binding by inhibiting upregulation of CD11b/CD18 on activated neutrophils. Accordingly, pioglitazone may be useful for treating inflammatory diseases. [source] Effects of an antiatherogenic diet during pregnancy on markers of maternal and fetal endothelial activation and inflammation: the CARRDIP studyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 3 2007J Khoury Objective, To study the effect of an antiatherogenic diet on maternal and cord blood concentrations of systemic biomarkers of endothelial cell activation, haemostasis and inflammation. Design, Single blinded randomised controlled clinical trial. Setting, Obstetric outpatient clinic and maternity unit of a university hospital in Norway. Population, Nonsmoking pregnant women aged 21,38 years carrying a single fetus and with no previous pregnancy-related complications. Methods, Subjects (n = 290) were randomised to continue their usual diet or to adopt a diet low in saturated fat and cholesterol from gestational week 17,20 to birth. Soluble forms of cellular adhesion molecules, high-sensitivity C-reactive protein (CRP) and haemostatic markers were measured at 17,20 weeks of gestation (baseline) and subsequently up to week 36. All the above, except CRP, were also measured in cord blood. Main outcome measures, Concentrations of maternal and fetal biomarkers and maternal CRP. Results, All biomarkers except CRP levels increased significantly during the study period in both the intervention and control groups. None of the maternal or fetal biomarkers were influenced by the intervention (P > 0.05) except for a tendency to lower concentrations of cord blood tissue plasminogen activator antigen in the intervention group compared with the control group, median (interquartile range) 5.4 ng/ml (3.1,7.7) versus 5.8 ng/ml (3.5,11.8), P = 0.05. Conclusion, An antiatherogenic diet in pregnancy did not significantly influence maternal or fetal blood concentrations of a range of biomarkers for inflammation. Thus, the previously reported effects of a cholesterol-lowering diet on maternal lipid profile and preterm delivery (<37 complete weeks of gestation) do not seem to involve changes in the systemic inflammatory responses of pregnancy. [source] | ||||||||||