Platelet‐activating factor (PAF) plays an important role in the immediate asthmatic response in guinea‐pig by augmenting the response to histamine

Abstract

1 To investigate the role of platelet activating factor (PAF) in the immediate asthmatic response, we examined the bronchial reactivity to histamine after administration of PAF to guinea-pigs or antigen challenge to passively sensitized guinea-pigs. 2 A bolus injection of PAF (20-40ngkg-1), which did not cause a significant increase in intrathoracic pressure (ITP), augmented the bronchial response to histamine almost 8 fold. This airway hyperreactivity was observed even 1 min after PAF treatment. 3 A subthreshold dose of antigen (0.01 mg kg 1, i.v.) also provoked hyperreactivity to histamine, which became significant 6 and 11 min after the antigen treatment. 4 The specific PAF-antagonists, SM-10661 and CV-6209 (i.v.) dose-dependently inhibited both PAFand antigen-induced airway hyperreactivities to histamine. 5 These results suggest that PAF plays an important role in antigen-induced acute airway responses by augmenting the activities of spasmogens.

Inhibition of leukotriene formation and IL-8 release by the PAF-receptor antagonist SM-12502

“…In this regard, our data clearly demonstrate that the phospholipid mediator PAF is intimately involved in the regulation of leukotriene and cytokine synthesis, and as was described by Morooka et al (40) in histamine release.…”

Effect of the PAF-receptor antagonist SM-12502 on human platelets

“…Recently, autocrine and paracrine regulatory mechanisms have been described among these mediators (30)(31)(32)(33)(34). The phospholipid mediator PAF is intimately involved in this regulatory network (29,35). The molecular mechanisms by which PAF exerts its autocrine effects are still not completely elucidated.…”

Contribution of thromboxane A2 to the antigen‐induced immediate asthmatic response mediated by IgG1 antibody by augmentation of bronchial responsiveness in guinea‐pigs

“…ACh induced by inhalation of bacterial lipopolysaccharide in guinea-pigs (Arimura et al, 1993) is similar to that required for the inhibition of IgGI-mediated bronchoconstriction. Morooka et al (1991) have demonstrated that the doses of a platelet-activating factor (PAF) antagonist required to suppressed antigen-induced airway hyperreactivity were more than 100 times higher than the dose required to inhibit PAF-induced responses. These findings lead to the Acetylcholine (A.g kg-', i.v.)…”