Excessive respiratory glycoprotein secretion occurs in a variety of inflammatory States: A variety of lipid inflammatory mediators have been demonstrated to have a stimulatory effect on secretion in human and experimental animal studies in an in vitro airway organ culture system. The role of Platelet Activating Factor (PAF) on respiratory glycoprotein secretion and the mechanism of its effect have not been well described. PAF stimulates glycoprotein secretion in a dose response fashion. This response is inhibited by a specific PAF receptor antagonist and is also inhibitable by inhibitors of the lipoxygenase pathway of eicosanoid metabolism. Studies of specific eicosanoid metabolites suggests that PAF induces selective production of lipoxgenase and cyclooxygenase pathway metabolites and that the effect of PAF on airway secretion is mediated by the production of these metabolites. The effect of PAF on airway secretion is now published. The capacity of PAF to induce eicosanoid generation from airway explants and airway epithelial cells in culture is the subject of ongoing studies and of a manuscript in-preparation. The mechanism of signal transduction by which TAF activates PLA2 is under investigation via PAF activation of PLA2 and PA induced generation of a variety of a PAF receptor on epithelial cells eicosanoids by airway epithelial cells is the subject of a manuscript now in press. The activities of this project are now combined with other under Z01-CL- 00132-02-CCM The importance of these studies is that they lay the groundwork for the development of new therapies for inflammatory diseases of the lung.
