Inflammatory actions of platelet activating factor (Paf‐acether) in guinea‐pig skin

1 Cutaneous responses to synthetic platelet activating factor (Paf‐acether) have been studied in guinea‐pigs by means of radioisotopic marker techniques. 2 Intradermal injection of Paf‐acether elicited increased plasma protein extravasation (IPPE) (0.2–200 pmol/site), platelet accumulation (PA) (20–200 pmol/site) and red blood cell accumulation (RBCA) (200 pmol/site), whereas lyso‐Paf (up to 2 nmol/site) was inactive in all these respects. 3 Following intradermal injection, the IPPE responses to Paf‐acether (2 and 20 pmol/site) were complete within 15 and 30 min respectively, although in response to 200 pmol/site, IPPE was detectable up to 1.5 h. The PA and RBCA responses to Paf‐acether (200 pmol/site) were complete within 1 h. 4 IPPE induced by Paf‐acether (3 pmol/site) was potentiated by concomitant intradermal injection of a cutaneous vasodilator prostaglandin E2 (PGE2, 1 nmol/site) and inhibited by the β‐adrenoceptor agonist, isoprenaline (4.5 nmol/site) or the α‐adrenoceptor agonist, phenylephrine (6 nmol/site). Such observations are consistent with Paf‐acether effecting increased vessel wall permeability. 5 Intradermal injection of PGEx (3 nmol/site) significantly reduced PA in response to Paf‐acether (200 pmol/site), whilst significantly enhancing IPPE. This dissociation of increased vascular permeability from PA is consistent with Paf‐acether eliciting IPPE via a platelet‐independent mechanism. 6 These results indicate that a direct effect on vessel wall permeability contributes to the inflammatory response to Paf‐acether in guinea‐pig skin. It is suggested that Paf‐acether is a potential mediator of allergy and inflammation.