Pathophysiologic changes induced by phospholipase A2 in the isolated, perfused guinea pig lung.
Pathophysiologic changes induced by phospholipase A2 (PLA2), a lipolytic enzyme implicated in a variety of pulmonary diseases, were examined in the isolated, perfused guinea pig lung. Thirty microliters of vehicle (saline) or 30 units of PLA2 suspended in saline was given as a bolus injection into either the trachea or pulmonary artery, and the lungs were examined by combined light and transmission electron microscopy at 1, 10, and 30 min following administration. Pulmonary morphologic and physiologic changes were observed only in animals that received PLA2 via the trachea. Initially, morphologic evidence of airway constriction was accompanied by a significant increase in intratracheal pressure. No morphologic change was observed in alveolar parenchymal cell populations at this time. Later there was marked swelling of airway epithelial cells accompanied by pronounced blebbing of the apical cytoplasm with a subsequent decrease in airway lumen size. Interalveolar septa were multifocally thickened by edema and alveolar spaces contained sparse fibrogranular material 10 min after intratracheal PLA2. Significant increases in lung weight were observed at this time. Morphologic features of vasoconstriction, characterized by undulating and convoluted endothelium with prominent cytoplasmic processes resulting in decreased luminal size were observed in small caliber vessels and occurred in conjunction with significant increases in pulmonary arterial pressure. There was pronounced injury to type I alveolar epithelium, including marked cell swelling and fragmentation, accompanied by lesser injury in type II alveolar epithelium. This study demonstrates that the airway epithelium was the initial cell population having morphologic change following intratracheal PLA2, and that the airway epithelium and type I alveolar epithelium were the cell populations most severely affected following intratracheal PLA2. Results further suggest that normal circulating levels of blood-formed elements are not essential for the development of PLA2-induced morphologic change in the isolated, perfused guinea pig lung.
Department of Toxicology, Hoffmann-La Roche, Nutley, New Jersey 07110-1199.
S K
SK
Durham
W M
WM
Selig
D000818:Animals; D004848:Epithelium / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010477:Perfusion; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D054467:Phospholipases A2; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D014132:Trachea
D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2