Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eosinophils (EOs) participate in a variety of inflammatory states characterized by endothelial cell damage, such as vasculitis, pneumonitis, and endocarditis. We find that 100 U/ml TNF-alpha/cachectin (TNF), a concentration attainable in the blood of humans with parasitic infestations, stimulates highly purified populations of EOs to damage human umbilical vein endothelial cells (HUVEC), a model of human endothelium. This TNF-dependent EO cytotoxicity is strongly inhibited by heparin and methyprednisolone but unaffected by the platelet-activating factor antagonist BN52012 or scavengers of superoxide anion and H2O2, superoxide dismutase and catalase. However, addition of a physiologically relevant concentration of Br- (100 microM) enhances EO/TNF damage to HUVEC, implicating the possible participation of EO peroxidase (EPO) in the killing mechanism. EOs adherent to FCS-coated plastic wells more than double their production of superoxide anion and the cytotoxic EPO-derived oxidant HOBr when exposed to TNF, showing that TNF activates the respiratory burst of EOs attached to a "physiologic" surface. Unlike PMNs, EOs were not irreversibly activated to kill unopsonized endothelium by previous exposure to TNF, and did not degranulate or upregulate CR3 expression as detected by Mo1 in the presence of 100 U/ml TNF. HUVEC exposed 18 h to TNF were considerably more susceptible to lysis by PMA-activated EOs and reagent H2O2, demonstrating a direct effect of TNF upon endothelium, perhaps through inhibition of antioxidant defenses. These findings suggest that abnormally elevated serum levels of TNF may provoke EOs to damage endothelial cells and thereby play a role in the pathogenesis of tissue damage in hypereosinophilic states.
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PMID:Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. 197 79

The prevalence of antineutrophil cytoplasmic antibodies (ANCAs) was verified in 338 patients with various rheumatic diseases using the internationally standardized indirect immunofluorescence method. The method was improved by using ethidium bromide as a nuclear counterstain. We observed three patterns of fluorescence: the classical diffuse cytoplasmic granular staining (C); the perinuclear one (P) and a yet undescribed atypical cytoplasmic distribution (A). We thus found ANCAs in 14/15 (93%) patients with active Wegener's granulomatosis: 13 were C-ANCAs, 1 was P-ANCA. We also found ANCAs in 6/25 (22%) patients with other systemis vasculitides (essentially those with small vessel vasculitis): they were C-ANCAs (3 cases) or P-ANCAs (3 cases). Finally, ANCAs were detected in 10/185 patients with various autoimmune diseases (5 with rheumatoid arthritis and 5 with systemic lupus erythematosus): they were C-ANCAs (1 case), P-ANCAs (4 cases) or A-ANCAs (5 cases). No ANCAs were found in 100 control patients with miscellaneous diseases. The isotype distribution of ANCAs is essentially limited to IgG classes and the serum titre usually reflects disease activity. The technical improvement facilitates the distinction of ANCAs from other antinuclear and anticytoplasmic autoantibodies found in connective tissue diseases. Our data emphasize the clinical importance of ANCA detection and justify our efforts to develop more specific and quantitative assays.
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PMID:[Antineutrophil cytoplasmic antibodies in human pathologies]. 849 37

Recently, the possibility of direct involvement of the membrane attack complex of complement in the endothelial damage of immune complex vasculitis has been pointed out. However, no studies have so far elucidated this mechanism. The present study investigated the effects of complement on the membrane integrity of endothelial cells, using the fluorescein diacetate and ethidium bromide staining method. Cultured human umbilical vein endothelial cells were maintained in medium containing 10% zymosan-activated normal human serum. Cell detachment began to occur after 3 h of incubation, and the number of fluorescein diacetate-positive adherent cells decreased significantly, whereas that of ethidium bromide-positive detached cells increased significantly. Heat inactivation of the serum or replacement of the complement source with non-activated normal human serum or C5-, C7- or C9-deficient serum resulted in complete inhibition of these effects. These results suggest that complement induces detachment of endothelial cells by altering the cell membrane integrity and support the contention that the membrane attack complex of complement plays a significant role in the mechanisms of endothelial cell damage in immune complex vasculitis.
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PMID:The membrane attack complex of complement alters the membrane integrity of cultured endothelial cells: a possible pathophysiology for immune complex vasculitis. 872 82

Vinorebine (VNR), a second-generation vinca alkaloid antitumor drug, caused serious local venous toxicities, such as venous irritation, phlebitis and necrotizing vasculitis. This study investigated whether resveratrol (RES), a naturally occurring polyphenol compound, could reduce the vascular injury induced by VNR. Human vascular endothelial cell line ECV-304 cells were exposed to VNR for 10 min and then cells were cultured with serum-free medium with or without RES for 24 h. MTT (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphe-nyl-2-tetrazolium bromide) assay was used to detect the cell viability. Reactive oxygen species (ROS) was measured with 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The activity of superoxide dismutase (SOD) was assessed by SOD detection kit. VNR decreased the viability of ECV-304 cells in a dose-dependent manner. Moreover, VNR caused cell apoptosis, the generation of intracellular ROS and the reduction of intracellular SOD. Interestingly, pretreatment with RES for 2 h increased the cell viability in a dose-dependent manner. Cell apoptosis, the intracellular ROS generation and the reduction of intracellular SOD induced by VNR were also attenuated when cells were pretreated with RES for 2 h. These results demonstrated that RES would protect against vascular endothelial cell injury induced by VNR. So the use of RES together with VNR may be a possible therapeutic approach to avoid the vascular injury induced by VNR.
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PMID:Resveratrol protects against vinorelbine-induced vascular endothelial cell injury. 2397 33