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)

Neutrophils from patients suffering from severe congenital neutropenia (SCN), who were receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF), were investigated in order to analyze the previously described decrease in chemotaxis. This study demonstrated the decreased chemotaxis to five well-known chemoattractants, FMLP, C5a, IL-8, LTB4 and PAF. To further investigate this impairment of patients' neutrophils, receptors and receptor turnover for chemoattractants were examined using flow cytometry. We found 1) increased FMLP receptor and decreased C5a receptor expression, 2) a normal expression of intracellular FMLP receptors after incubation with PMA, 3) increased loss and decreased re-expression of FMLP receptors after incubation with this peptide, 4) normal expression of adhesion glycoproteins CR3 (CD11b/CD18) and LFA1 (CD11a/CD18), 5) further signs of in vivo preactivation: high expression of Fc gamma-RI (CD64) and Fc gamma-RII (CD32), decreased expression of Fc gamma-RIII (CD16), increased expression of CD14, and low expression of HLA-DR. These data demonstrate that the decrease of chemotaxis of neutrophils from SCN patients is not due: a) to a decrease in the number of intra- or extracellular FMLP receptors; b) to a decrease of adhesion molecules. However, the decreased chemotaxis could result from an altered FMLP receptor turnover. The relevance of the altered Fc gamma-receptor pattern for the in vivo occurrence of side-effects, e.g. the necrotic vasculitis, of G-CSF treatment is discussed.
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PMID:Altered function and surface marker expression of neutrophils induced by rhG-CSF treatment in severe congenital neutropenia. 137 Apr 19

Histological analysis of lung and kidney after multiple PAF i.v. injection into rabbits was performed. Under these conditions the effect of previously injected of verapamyl, calcium channel blocker, was studied. It was shown that RAF causes inflammatory reaction with cell infiltration, microcirculation disorders and thrombosis in lung and kidney, which may classify as interstitial nephritis, pneumonitis and vasculitis. Verapamyl inhibits vasospasm, abolishes fibrinogen but does not affect cell infiltration and oedema development. Thus, Ca channel-dependent mechanism of vasospasm and thrombogenesis induced by PAF in vivo is confirmed. Perhaps, another possibilities for realising PAF action in vivo may occur.
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PMID:[A morphologic analysis of changes in the lungs and kidneys caused by acetyl glyceryl ether phosphorylcholine and limited by verapamil]. 261 82

Platelets-isolated or in conjunction with leukocytes-interact with vessel walls in many experimental and human diseases. Several mediators are held responsible for platelet activation and interaction with leukocytes, among which PAF-acether (platelet-activating factor) is a prime candidate. This phospholipid mediator is released by most inflammatory cells, including neutrophils, by isolated organs such as kidney and heart, is a potent platelet and neutrophil agonist, and exerts major vasoactive properties. Its biosynthesis involves a two-step enzymatic process yielding the active molecule from the membrane alkyl-ether choline-containing phospholipids. The first step implicates a phospholipase A2 that hydrolyzes a long-chain fatty acid (which can be arachidonic acid) from membrane phospholipids, leaving the intermediate compound lyso PAF-acether, a PAF-acether precursor that is acetylated by an acetyltransferase in a second step. It can also result from deacetylation of PAF-acether by an acetylhydrolase. PAF-acether release might explain the intervention of platelets in diseases such as glomerulonephritis and allergic vasculitis, in which the involvement of neutrophils and platelets is frequently noted. The end result of these complex sets of cell-to-cell interactions is the release of most known inflammatory mediators, influencing vascular permeability, cell infiltration, and smooth muscle contraction. Nevertheless, direct evidence for the implication of these rather well-defined cellular and molecular interactions in human pathologic states remains to be obtained.
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PMID:A role for PAF-acether (platelet-activating factor) in platelet-dependent vascular diseases? 392 92

1. Mediators of inflammation can increase vascular permeability in at least two different ways: by acting directly on endothelial cells or, indirectly, through an incompletely understood mechanism, dependent on circulating neutrophils. Neutrophil-dependent oedema formation has been described in the skin of rabbits, rats, hamsters, mice and man. In contrast, we presented evidence in a previous study that local oedema formation induced by i.d. injection of chemoattractants in guinea-pig skin was neutrophil-independent. In the present study, we sought evidence of neutrophil-dependent oedema formation in immune-complex-mediated vasculitis, the reversed passive Arthus (RPA) reaction, in guinea-pig skin. We also investigated whether haemorrhage in the RPA reaction was neutrophil-dependent (as it is in other species) and the role of endogenous mediators of inflammation (prostaglandins, nitric oxide, histamine, PAF and leukotrienes) in contributing to the local inflammatory response. 2. In the RPA reaction, most oedema formation occurred over the first 60 min whereas 111In-neutrophil accumulation was still increasing from 60 to 240 min. The different kinetics of these two events suggested that they may be dissociated. 3. Oedema formation was partially inhibited by a long-acting PAF antagonist (UK-74,505) and an H1 histamine receptor antagonist (mepyramine) but not by a 5-lipoxygenase inhibitor (ZM 230487). A nitric oxide synthesis inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) suppressed oedema formation by 68% whereas a cyclo-oxygenase inhibitor suppressed oedema by 27%. 4. 111In-neutrophil accumulation in the RPA reaction was partially suppressed by UK-74,505. In contrast, ZM 230487 was without effect at doses which abrogated arachidonic acid-induced 111In-neutrophil accumulation. 5. The anti-CD18 monoclonal antibody, (mAb) 6.5E F(ab')2, effectively inhibited 111In-neutrophil accumulation induced by PAF, zymosan-activated plasma (ZAP) and in the RPA reaction. However, oedema formation measured in the same sites was not altered. In contrast, oedema formation in the RPA reaction was partially suppressed by 6.5E whole mAb which was 2.5 times more potent than 6.5EF(ab')2 at inhibiting guinea-pig neutrophil adhesion to protein-coated plastic. Haemorrhage induced by PAF and in the RPA reaction was significantly inhibited by 6.5E F(ab')2 pretreatment.6. We conclude that in the RPA reaction in guinea-pig skin, oedema formation is partially neutrophil dependent as assessed by using an anti-CD18 mAb, whereas ZAP-induced oedema formation is neutrophil-independent. Haemorrhage was also dependent on neutrophil accumulation. In addition, our studies support a role for PAF in mediating both oedema formation and "'In-neutrophil accumulation in the RPA reaction. Endogenous release of histamine also appears to be important in mediating oedema formation suggesting that mast cells play a critical role in increases of vascular permeability in inflammatory reactions in guinea-pig skin. Moreover, our results confirm previous findings which suggest a dominant role for nitric oxide in maintaining cutaneous blood flow in the guinea-pig.
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PMID:Studies on the mechanisms involved in the inflammatory response in a reversed passive Arthus reaction in guinea-pig skin: contribution of neutrophils and endogenous mediators. 788 93