Role of PAF in the allergic pleurisy caused by ovalbumin in actively sensitized rats.
Selective platelet-activating factor (PAF) antagonists and autodesensitization to this lipid were used to investigate the role of PAF in antigen-induced pleurisy in the rat. Pleural inflammation was triggered by the intrathoracic (i.t.) injection of ovalbumin (12 micrograms/cavity) into animals actively sensitized 14 days before. Successive daily i.t. injections of PAF (1 microgram/cavity) led to selective autodesensitization, which was apparent after the third injection and maximal after the fifth. The PAF antagonists BN 52021 and WEB 2086 inhibited the late pleural eosinophil accumulation caused by antigen but, as also noted with WEB 2170, failed to modify the early antigen-induced plasma exudation and leukocyte infiltration. In contrast to the antagonists, desensitization to PAF was clearly effective against these early alterations. To further investigate this discrepancy, the antigenic challenge was performed 24 h after a single prestimulation with PAF, when sensitivity to the lipid was still intact. Under this condition, plasma exudation and cellular influx triggered by the antigen were also abrogated, indicating that this protective effect was accounted for by a mechanism other than refractoriness to PAF. Because 24 h after PAF injection only eosinophil counts remained elevated, an alternative eosinophilotactic substance was used to further study the mechanism of PAF versus antigen-induced pleural inflammation. Prior treatment with the peptide Ala-Gly-Ser-Glu (ECF-A, 20 micrograms/cavity) also inhibited the allergic pleurisy, whereas the noneosinophilotactic substances histamine (200 micrograms/cavity) and serotonin (100 micrograms/cavity) were inactive. Furthermore, drugs that share the ability to impair PAF-induced eosinophilia, including azelastine and cetirizine, prevented the inhibitory effect of PAF on the antigen-induced pleurisy. These findings suggest that PAF may account for the late eosinophilia, but not for the acute phase of the rat allergic pleurisy, which is clearly attenuated by PAF or ECF-A pretreatment.
Martins
M A
MA
Departamento de Fisiologia e Farmacodinâmica, Rio de Janeiro, Brazil.
Castro Faria Neto
H C
HC
Bozza
P T
PT
e Silva
P M
PM
Lima
M C
MC
Cordeiro
R S
RS
Vargaftig
B B
BB
D000704:Analysis of Variance; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology; D004224:Diterpenes; D004342:Drug Hypersensitivity; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D005620:Freund's Adjuvant; D046934:Ginkgolides; D007249:Inflammation; D007783:Lactones / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins; D010998:Pleurisy / Q000097:blood / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D002631:Chemotactic Factors, Eosinophil; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D009842:Oligopeptides; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; C063376:alanyl-glycyl-seryl-glutamic acid; D010047:Ovalbumin; D005620:Freund's Adjuvant; C045856:ginkgolide B