Role of paf-acether in the mediation of pathophysiological responses to aggregated immunoglobulins. Studies with the platelet-activating factor receptor antagonist BN 52021.
Sprague-Dawley rats were challenged with an intravenous (i.v.) infusion of soluble aggregates of immunoglobulin G. Animals receiving a dose of aggregates of 40 mg/kg showed a significantly reduced time of lysis of diluted blood clot, which paralleled the appearance in plasma of tissue-type plasminogen activator. These changes occurred about 5-10 min after the challenge, which is a more protracted time-course than that observed in response to paf-acether. A significant increase in serum levels of N-acetylglucosaminidase was also observed in the animals several minutes after challenge. Blood neutrophil count showed a 50% reduction that reached its maximum at 10 min and was followed by an overshoot after 30 min. In experiments in rats previously depleted of circulating PMN by treatment with vinblastine, no significant differences were observed in N-acetylglucosaminidase release as compared to non-treated animals. Since prior evidence indicated that endogenously generated paf-acether could be a mediator responsible for these changes, at least to some extent, the compound BN 52021, a specific antagonist of the paf-acether receptor was given to these animals prior to the challenge with the complexes. All the above mentioned responses were significantly reduced by BN 52021, which is in keeping with the hypothesis involving endogenous paf-acether release in the mediation of these changes. By contrast, BN 52021 did not interfere with the clearance of the aggregates from the circulation, which seems to be a beneficial mechanism to reduce immune-mediated tissue injury. These data extend the number of paf-acether mediated pathophysiological changes that can be observed in response to immune aggregates.
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D004224:Diterpenes; D046934:Ginkgolides; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D008657:Metabolic Clearance Rate; D009503:Neutropenia / Q000209:etiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D004224:Diterpenes; D046934:Ginkgolides; D007074:Immunoglobulin G; D007783:Lactones; D010972:Platelet Activating Factor; C044411:polymeric IgG; C045856:ginkgolide B; D000118:Acetylglucosaminidase; D010959:Tissue Plasminogen Activator