The long-term objective will be to characterize the pathobiology of acetyl glyceryl ether phosphorylcholine (AGEPC)-induced acute and/or chronic inflammatory pulmonary injury. AGEPC is a potent phospholipid mediator of inflammation; however, the precise role and mechanisms by which AGEPC initiates and promotes tissue injury in the lung remain to be established. Thus, the focus of the study will be to characterize the pulmonary alterations induced by the intravenous administration of AGEPC into rabbits relative to possible mechanisms involved in this process. These studies will focus upon AGEPC-induced cardiovascular and pulmonary physiologic alterations, pulmonary platelet and neutrophil sequestration and subsequent activation, alterations in pulmonary vascular permeability, and pulmonary tissue injury as assessed by light and electron microscopy. The effects of various interventions (AGEPC antagonists, inhibitors of arachidonic acid metabolism, and inflammatory cell depletion) on these parameters as they occur following AGEPC infusion will be temporally assessed. The effect of prolonged intravenous infusions of AGEPC upon these parameters also will be evaluated. Finally, AGEPC-like phospholipids from pulmonary tissues obtained during the course of allergic and inflammatory disease processes will be isolated and qualitatively and quantitatively characterized. The results of these studies will provide new information regarding the characteristics and mechanisms of AGEPC-induced pulmonary injury and may be useful for future studies designed to prevent or treat similar reactions as they may occur in allergic and inflammatory pulmonary diseases affecting man.
