Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet activating factor (PAF) has many proinflammatory properties. It is a polymorphonuclear leukocyte chemotactic factor, it aggregates platelets, increases vascular permeability, and is generated by inflammatory cells. To determine the possible in vivo role of PAF in inflammation, we examined the effects of the PAF antagonist and structural analogue, CV3988 on acute inflammatory responses in the skin of rabbits. Initial experiments indicated that CV3988 (10 mg/kg) was a specific inhibitor of PAF responses in vivo since it abolished neutropenia and thrombocytopenia induced by intravenous (iv) PAF infusion without effecting the response to f-met-leu-phe. In dermal inflammation, 125I-albumin, 111In-labeled platelets, 51Cr-labeled leukocytes, and 86RbCl were used to simultaneously quantitate protein exudation, platelet deposition, leukocyte accumulation, and blood flow in the lesions. CV3988 inhibited inflammatory responses to intradermal injection of PAF by 65 to 85% but it did not inhibit thrombin-induced platelet deposition or bradykinin and histamine-induced protein exudation. CV3988 treatment inhibited by 60 to 80% (p less than 0.01) the platelet deposition occurring at the peak of the reaction (1 1/2 hours) induced by the intradermal injection of zymosan, zymosan activated plasma, endotoxin, and the reversed passive Arthus reaction. Protein exudation was inhibited by 67 to 85% (p less than 0.1) and leukocyte accumulation was inhibited by 24 to 35% (p less than 0.05), but only in the zymosan and reversed passive Arthus reactions, respectively. Inflammatory hyperemia (increases blood flow) was not affected by CV3988 treatment. We conclude that in certain inflammatory reactions, PAF may mediate platelet deposition and protein exudation. The marginal effect of CV3988 on leukocyte accumulation suggests that the leukotactic activity of PAF is relatively less important in vivo.
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PMID:Evidence that platelet activating factor may mediate some acute inflammatory responses. Studies with the platelet-activating factor antagonist, CV3988. 395 Nov 99

A murine anti-rat intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody (mAb), 1A29, was used to investigate the importance of blood leukocyte-associated beta 2-integrin (CD11/CD18) vascular endothelium-associated ICAM-1 adhesive interactions in the reversed passive Arthus reaction (RPAR) in rats. An Arthus pleurisy reaction (4 h) was employed in these studies because it permits the accurate quantitation of polymorphonuclear neutrophil (PMN) influx into the pleural space and fluid accumulation. 1A29, which localized within Arthus lung lesions, caused a dose-dependent (0.5-2.0 mg/kg, i.v.) inhibition of PMN influx (19-56%) and exudate volume (9-55%) in the Arthus pleurisy reaction. P7 (2 mg/kg, i.v.), a murine anti-human P-selectin mAb used as an isotype-matched control for 1A29, did not localize at the lung lesion site and was inactive. Immunohistochemical analysis of lung tissue from 1A29-treated rats demonstrated increased granulocyte accumulation in the alveolar capillaries compared with more extensive granulocyte emigration into the lung tissue and pleural space in P7-treated rats and Arthus control rats; however, quantitative image analysis revealed increased numbers of lung granulocytes in 1A29-treated rats compared with controls. Neither ICAM-1 mRNA nor expression, assessed by immunocytochemistry, was increased above control levels in rats during the pleural Arthus reaction. Neutropenia was not observed in either 1A29- or P7-treated rats.
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PMID:ICAM-1 mediates leukocyte-endothelium adhesive interactions in the reversed passive Arthus reaction. 860 10

C5a is implicated as a pathogenic factor in a wide range of immunoinflammatory diseases, including sepsis and immune complex disease. Agents that antagonize the effects of C5a could be useful in these diseases. We have developed some novel C5a antagonists and have determined the acute anti-inflammatory properties of a new small molecule C5a receptor antagonist against C5a- and LPS-induced neutrophil adhesion and cytokine expression, as well as against some hallmarks of the reverse Arthus reaction in rats. We found that a single i.v. dose (1 mg/kg) of this antagonist inhibited both C5a- and LPS-induced neutropenia and elevated levels of circulating TNF-alpha, as well as polymorphonuclear leukocyte migration, increased TNF-alpha levels and vascular leakage at the site of immune complex deposition. These results indicate potent anti-inflammatory activities of a new C5a receptor antagonist and provide more evidence for a key early role for C5a in sepsis and the reverse Arthus reaction. The results support a role for antagonists of C5a receptors in the therapeutic intervention of immunoinflammatory disease states such as sepsis and immune complex disease.
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PMID:A new small molecule C5a receptor antagonist inhibits the reverse-passive Arthus reaction and endotoxic shock in rats. 1084 15