Phospholipase A2-induced pathophysiologic changes in the guinea pig lung.
The pathophysiology of lung injury induced by phospholipase A2 (PLA2), a lipolytic enzyme implicated in a variety of pulmonary diseases, was examined in the guinea pig. One hundred microliters of saline or 10 units of PLA2 suspended in saline was given as a bolus injection into either the trachea or jugular vein. Intratracheal pressure and mean arterial blood pressure were continuously monitored. The lungs were examined by light and transmission electron microscopy at 1, 10, and 30 minutes after administration. Pulmonary morphologic and physiologic changes were only observed in animals that received PLA2 via the trachea. Significant increases in peak intratracheal pressure occurred as early as 1 minute after intratracheal PLA2 administration. Morphologic evidence of airway constriction, accompanied by blebbing of the apical cytoplasm of airway epithelium, was also observed at this time. A transient increase in mean arterial blood pressure occurred 5 minutes after challenge. At 10 minutes after intratracheal PLA2, there was marked swelling of airway epithelial cells, pronounced blebbing of the apical cytoplasm, and a resultant decrease in size of the airway lumen. Morphologic changes in alveolar cell populations were initially observed 10 minutes after intratracheal PLA2. Interalveolar septa were hypercellular and multifocally thickened. There was prominent perivascular edema and alveolar spaces contained abundant proteinaceous material and occasional hemorrhage. Ultrastructurally, there was marked cell swelling and fragmentation of type I alveolar epithelium resulting in a denuded basal lamina. Sequestration of neutrophils and eosinophils, many of which lacked secretory granules, within alveolar capillaries was accompanied by aggregates of platelets and was observed in close proximity to injured endothelium. Morphologic changes indicative of cell injury were also observed in type II alveolar epithelium. Similar, but more frequent and severe, morphologic injury occurred 30 minutes after intratracheal PLA2. It is concluded that PLA2 induces pronounced morphologic and physiologic changes in the guinea pig and that the route of administration is important in the development of PLA2-induced lung injury.
Durham
S K
SK
Department of Toxicology and Pathology, Hoffmann-La Roche, Nutley, New Jersey 07110-1199.
Selig
W M
WM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D013997:Time Factors; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2