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)

Acute immune complex-mediated dermal vasculitis and pulmonary alveolitis have been induced in rats by the intradermal injection or intrapulmonary instillation of rabbit polyclonal antibody to bovine serum albumin (BSA), followed by intravenous injection of antigen. In the dermis, using reconstitution experiments in neutrophil-depleted rats and platelet-activating factor (PAF) receptor antagonists, we have shown that accessibility of PAF receptors on neutrophils is required for the full expression of dermal vascular injury. In the lung, intratracheal instillation of PAF receptor antagonists (with anti-BSA) results in a 54% suppression of pulmonary vascular leakage, suggesting that PAF receptors are necessary for the full expression of injury. These data suggest that in immune complex-induced tissue damage in which neutrophils and their oxygen radicals and proteases play a key role, there is an interplay of PAF and neutrophils required for the full expression of injury. The possible mechanisms involved will be discussed.
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PMID:PAF and immune complex-induced injury. 196 16

These studies were designed to determine the role of platelet-activating factor (PAF) in the pathogenesis of immune complex (IgG) induced dermal vasculitis in the rat. In vitro, very low (pM and nM) concentrations of PAF "primed" rat neutrophils for enhanced O2-. responses to IgG immune complexes while higher concentrations were directly stimulatory. The PAF receptor antagonist, L-652,731, blocked responses (O2-. production and enzyme release) of rat neutrophils stimulated with PAF but did not block responses triggered by immune complexes, formyl chemotactic peptide or opsonized zymosan particles. When L-652,731 was added to the antibody employed in the reversed passive Arthus reaction, the injury resulting from immune complex-induced vasculitis was significantly attenuated. In order to determine if in vivo protection provided by L-652,731 was related to neutrophils, we developed a new model in which rats are systemically depleted of neutrophils by cyclophosphamide and then locally reconstituted with intact neutrophils in a manner that allows restoration of immune complex-induced vascular injury. With this model, we demonstrated that the effects of neutrophil reconstitution are substantially diminished if the cells are pretreated with L-652,731 and then washed. By priming neutrophils with substimulatory concentrations of PAF, we have also provided in vivo evidence that neutrophil priming can increase the magnitude of vascular injury. These data provide evidence that vascular injury associated with immune complex dermal vasculitis is related to availability of PAF receptors on neutrophils, suggesting a mechanism through which PAF may function as a mediator in the pathogenesis of immune complex vasculitis.
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PMID:Evidence for the role of platelet-activating factor in immune complex vasculitis in the rat. 253 3

In a model of vasculitis we have evaluated mechanisms for how neutrophil polymorphonuclear granulocytes (PMNs) kill cultured human umbilical vein endothelial cells (HUVECs) in vitro (as release of chromium 51) in response to the double dioxygenation product of arachidonic acid, lipoxin A4 (LXA4) and to formyl-methionyl-leucyl-phenylalanine (fMLP). The cytolysis induced by LXA4 and fMLP was dose dependent, with maximum values at 100 nmol/L (which caused a 2.7-fold and 2.3-fold increases of 51Cr release, respectively, relative to buffer-treated controls). LXA4 also conferred a peak of cytotoxicity at 0.1 nmol/L (which caused a 2.2-fold increase in 51Cr release). Leukotriene B4, platelet activating factor (PAF), and zymosan-activated serum were inefficient. Phorbol myristate acetate caused the most prominent cytotoxicity, which was first evident at 1 mumol/L. The LXA4 effect was abrogated by superoxide dismutase, catalase, alpha 2-macroglobulin, and alpha 1-antitrypsin but not by mannitol. Addition of a monoclonal antibody (mAb) to CD18 also inhibited neutrophil-dependent cytotoxicity to LXA4 and fMLP. MAbs to intercellular adhesion molecule-1 or P-selectin blocked 100% and 52%, respectively, of the LXA4-induced cytotoxicity. Neutrophils from a patient with chronic granulomatous disease were incapable of mediating any cytotoxicity. The LXA4 effect was inhibited by the PAF receptor antagonist WEB-2086 and by treating neutrophils with pertussis toxin. Thus this novel effect of LXA4, as a potent promoter of neutrophil-mediated cytotoxicity for HUVECs, is a process dependent on PMN adhesion proteins, oxygen radicals, and proteases, and it is apparently associated with endogenous PAF expression and requires pertussis-sensitive G proteins.
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PMID:Mechanisms for lipoxin A4-induced neutrophil-dependent cytotoxicity for human endothelial cells. 760 32

Platelet-activating factor (PAF) is a phospholipid inflammatory mediator which is synthesized by a variety of cells, including monocytes, endothelial cells, mast cells and neutrophils. PAF acts via a recently cloned PAF receptor, present on monocytes and endothelial cells, but not on non-activated lymphocytes. IL-4 is mainly produced by T lymphocytes, and belongs to the Th2 subset of T helper cells. IL-6 is mainly a monocyte/macrophage-derived cytokine with multiple proinflammatory effects. We here report that PAF induces IL-4 production, as determined by ELISPOT. Antibodies to MHC class II inhibited the IL-4 stimulatory effects of PAF. PAF also had the capacity to induce IgA production, as determined by ELISPOT, and IL-6 production in peripheral blood mononuclear cells (PBMC) as determined by ELISA. These PAF-mediated effects were completely inhibited by a specific PAF-receptor antagonist, WEB 2170. Taken together, our data indicate that PAF activates T lymphocytes to IL-4 production by an indirect, monocyte-dependent mechanism dependent on MHC class II. PAF also enhances antibody formation and IL-6 production from PBMC. These findings indicate that PAF activates immune-competent cells, which may be of importance in inflammatory diseases such as asthma, vasculitis and atherosclerosis.
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PMID:Induction of IL-4 by platelet-activating factor. 887 Jul 12

Platelet activating factor (PAF) is a phospholipid with proinflammatory and thrombogenic properties, which has been implicated in inflammatory disorders including vasculitis and asthma. PAF-like compounds are present in oxidized LDL (oxLDL), which has been detected in the atherosclerotic lesion, where it may activate monocytes, macrophages, and T cells. OxLDL may therefore both initiate and perpetuate inflammatory reactions in the artery wall. Herein we demonstrate that PAF has the capacity to induce enhanced interferon gamma (IFN-gamma) secretion in peripheral blood mononuclear leukocytes (PBMCs), as does oxLDL. Both oxLDL- and PAF-induced IFN-gamma secretions were inhibited by a specific PAF-receptor antagonist, WEB 2170. PAF-like lipids in oxLDL could thus be responsible for oxLDL-induced activation of immune-competent cells. The effects of PAF and oxLDL were inhibited by antibodies to major histocompatibility complex class II and thus depend on accessory cells like monocytes. Both PAF and oxLDL induced tumor necrosis factor-alpha (TNF-alpha) synthesis in peripheral blood. PAF-mediated TNF-alpha production was inhibited by WEB 2170, whereas oxLDL-induced TNF-alpha was only partially inhibited. These findings indicate that both PAF and oxLDL have the capacity to induce TNF-alpha, which may increase atherogenesis due to its pleiotropic proinflammatory effects. Our findings suggest that the PAF receptor plays an important role in the inflammatory component of atherosclerosis.
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PMID:Platelet-activating factor and oxidized LDL induce immune activation by a common mechanism. 915 62