PAF-induced conjunctivitis in the rabbit is mediated by peptido-leukotrienes

Platelet activating factor (PAF) released by many cell types is involved in several steps of inflammatory reactions in various organs including the eye. It has been reported that some effects of PAF could be mediated by arachidonic acid metabolites generated after PAF-receptor interaction. In the study we investigated the protective effect of CBS-113A, a dual inhibitor of 5-lipoxygenase/cyclooxygenase in PAF-induced conjunctivitis in the rabbit. Moreover, the characterization of the icosanoid potentially mediating the PAF activity has been performed by using specific pharmacological agents. Subconjunctival injection of PAF (10-1000 ng) provoked Evans' blue extravasation measured in tissues within 30 min. Simultaneous injection of a PAF antagonist (BN 50730) inhibited the dye leakage, showing specific PAF receptor-mediated vascular reaction. CBS-113A applied in eye drops also inhibited Evans' blue extravasation. By contrast, indometacin administered either topically or by subconjunctival injection was not effective in reducing the effect of PAF. These results suggesting the involvement of a 5-lipoxygenase metabolite were confirmed by the effectiveness of local injection of SKF 104353, a specific leukotriene D4 antagonist. The present study shows that PAF-induced plasma leakage in conjunctivitis is mediated by peptido-leukotrienes.