Kinetics of acetyl glyceryl ether phosphorylcholine (AGEPC)-induced acute lung alterations in the rabbit

Abstract

Acetyl glyceryl ether phosphorylcholine (AGEPC; 1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) was infused intravenously into rabbits (0.5 micrograms/kg); subsequently, temporal pulmonary alterations were assessed histologically. Within 30 seconds after AGEPC infusion, widespread platelet and neutrophil aggregates were distributed throughout the pulmonary microvasculature. Concomitantly, small muscular arteries and bronchioles throughout the lungs were contracted. Five minutes after AGEPC infusion, intravascular pulmonary platelet aggregates were less frequent and smaller than those observed at 30 seconds after infusion; however, AGEPC-induced pulmonary neutrophil sequestration persisted. Moreover, at this time, large mononucleated cells and damaged endothelial cells were prevalent throughout the pulmonary microvasculature. Sixty minutes after infusion, neither platelet aggregates nor arterial or bronchiolar constriction was observed. However, in most animals, neutrophils and large mononucleated cells were still abundant, and focal endothelial cell alterations persisted. In addition, discrete areas of interstitial hemorrhage around small and medium-sized arteries were present. These studies suggest that the intravascular release of AGEPC could initiate significant pulmonary injury and therefore could be an important etiologic factor in the development of inflammatory lung diseases.