PAF ANTAGONISM AND THE RESPONSE TO ALLERGEN

 

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Intravenous infusion of platelet activating factor (PAF) causes platelets to aggregate and accumulate within the lung. A similar effect is observed when allergen is injected into sensitised animals. Since PAF is released in allergic reactions, it might be considered to be a mediator of this phenomenon. Intrathoracic accumulation of 111-Indium labelled platelets was detected by use of collimated sodium iodide crystal detectors as a part of an automated isotope monitoring system (AIMS 8000, Mumed ltd.). Intravenous infusion of PAF (600 ng/kg/h) caused progressive increase of the intrathoracic platelet content (TPC) (59%). Infusion of small doses of allergen (BGG, 300 ug/kg/h) produced comparable increase of TPC, whether animals were sensitised actively (1 mg/kg BGG+FCA i.p. and boosted two weeks later) (30%) or passively (i.v. injection of 0.25 ml anti-BGG serum) (53%) or received intravenous injections of preformed immune complexes. At a dose of 2 mg/kg/h, ginkgolide B (−5%) or kadsuranone (−1%) fully inhibited increased TPC in response to PAF. However, at higher doses (6 mg/kg/h) ginkgolide B did not diminish TPC in animals that were actively (33%) or passively (60%) sensitised, nor did kadsuranone (6 mg/kg/h) diminish the response in passively sensitised animals (42%) compared to vehicle animals (43%). These observations can be extended to acute bronchospasm and airway hyperreactivity which are secondary to platelet activation in these animals. It can be concluded that PAF formation appears to be a minor determinant of the acute response to allergen in the guinea-pig.