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Circulating Leukocytes (circulating + leukocyte)
Selected AbstractsSuppression of experimental lupus nephritis by aberrant expression of the soluble E-selectin genePATHOLOGY INTERNATIONAL, Issue 3 2002Satoru Takahashi Circulating leukocytes, particularly neutrophils and monocytes, are important effector cells in the induction of many forms of glomerulonephritis. Adhesion molecules, especially selectins, are also thought to be critical for the development of this disease. We examined the possible suppressive effect of soluble E-selectin on the development of experimental lupus nephritis induced by the injection of a hybridoma clone (2B11.3) derived from an MRL/MpJ- lpr/lpr lupus mouse. This clone produces IgG3 antibodies that induce severe proliferative glomerulonephritis resembling lupus nephritis when injected into normal mice. Transgenic mice with a soluble E-selectin gene were injected intraperitoneally with the hybridoma cells and histopathologically examined on day 15. As a result, the development of glomerulonephritis was significantly suppressed. This suppression was characterized by fewer inflammatory cell infiltrates, compared with non-transgenic litter mates, despite the fact that there were no remarkable differences in immunoglobulin deposits or expression of E-selectin between the two groups. These findings suggest that by controlling inflammatory cell infiltration, soluble E-selectin plays a preventative role in the development of a particular type of lupus nephritis. [source] Transient leukopenia and anaphylatoxin production during granulocyte apheresis as treatment for ulcerative colitisJOURNAL OF CLINICAL APHERESIS, Issue 3 2002Katsuhiko Yonemura Abstract It is well known that transient leukopenia due to activation of the alternative pathway of the complement system accompanies hemodialysis when cellulose acetate dialyzers are used. However, it has not been evaluated whether leukopenia also occurs during granulocyte apheresis (GCAP) as treatment for ulcerative colitis, in which an extracorporeal column is filled with cellulose acetate beads in order to remove circulating leukocytes. The aim of the present study was to evaluate whether transient leukopenia and activation of the alternative pathway of the complement system were observed during GCAP. In 8 patients undergoing GCAP weekly for 10 weeks, circulating leukocyte counts and plasma concentrations of C3a, a product of the activated alternative pathway of the complement system, were determined. GCAP elicited a rapid decline in the number of circulating leukocytes to 61.8 ± 13.8% of the baseline value after 15 minutes of GCAP (P < 0.02). Thereafter, the number of circulating leukocytes returned to approximately baseline after 60 minutes. The baseline plasma C3a concentration was 123 ± 61 ng/mL, and a significant increase to 425 ± 123 ng/mL was observed after 15 minutes of GCAP (P < 0.02). The plasma C3a concentration reached 417 ± 96 ng/mL after 60 minutes (P < 0.02). It thus follows that GCAP activates the alternative pathway of the complement system, resulting in anaphylatoxin production. J. Clin. Apheresis 17:107,110, 2002. © 2002 Wiley-Liss, Inc. [source] The role of the fibrocyte in intimal hyperplasiaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2006R. L. VARCOE Summary.,Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow-derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. Objectives: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. Methods and results: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha-smooth muscle actin (, -SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and , -SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and , -SMA) and also to double stain for CD34 and , -SMA. Conclusions: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury. [source] The Pancreas as a Source of Cardiovascular Cell Activating FactorsMICROCIRCULATION, Issue 3 2000ERIK B. KISTLER ABSTRACT Objective: Physiological shock leads to elevated levels of plasma factors that activate circulating leukocytes and endothelial cells, thereby compromising microvascular functions. The nature and source of these plasma-derived activators are unknown. To examine the possible origin of these factors, we homogenized rat internal organs and measured their activity on cardiovascular cells in vivo and in vitro. Methods: Fresh tissue samples from small intestine, spleen, heart, liver, kidney, adrenals, and pancreas were homogenized. Their ability to induce leukocyte pseudopod formation and nitroblue tetrazolium (NBT) reduction was tested and their impact in vivo on blood pressure, survival, and microvascular cell injury was examined. Results: A dramatic increase (p < 0.001) in leukocyte activation compared to controls was observed with pancreas homogenate but not with homogenates from the other organs. Leukocyte activation was induced by homogenates of other tissues only after prior incubation with substimulatory concentrations of pancreatic homogenate. Pancreatic serine proteases, trypsin and chymotrypsin, which did not stimulate leukocytes, also generated activity from other tissues. Leukocyte pseudopod formation could be significantly inhibited by adding the serine protease inhibitor 6-amidino-2-naphthyl p -guanidinobenzoate dimethanesulfonate (ANGD) during tissue homogenization (p < 0.001). Injection of pancreatic homogenate into rats led to increased plasma hydrogen peroxide levels and an instantaneous drop in mean arterial pressure that was often lethal. These responses were prevented by prior infusion of ANGD (p < 0.001). Intravital microscopy of the rat mesentery confirmed that superfusion of filtered pancreatic homogenate leads to significant increases in cell death (p < 0.05), as detected by propidium iodide, and hydrogen peroxide formation (p < 0.05), as determined by dichlorofluorescein diacetate (DCFH) fluorescence. Conclusion: These results suggest that pancreatic enzymes attack tissue and generate cellular activators that are associated with organ dysfunction in shock. [source] | ||||||||||