Endotoxin protection of rats from oxygen toxicity: role of lung phagocytes

Abstract

Endotoxin (1 mg/kg body weight, i.p.) greatly reduces lung damage and pleural edema in rats exposed to > 99% oxygen. Endotoxin also activates and depletes complement in vitro. Both complement and polymorphonuclear leukocytes (PMN) have been shown to play a role in the development of lung damage in several models of lung inflammation. PMN may injure tissue by releasing free radicals or proteolytic enzymes. This dissertation was designed to evaluate the possibility that the mechanism of endotoxin protection involves changes in either 1) the number of PMN or their ability to release free radicals or 2) serum complement levels following exposure of rats to > 99% oxygen for up to 3 days at 1 ata (sea level). The potential of 1avaged phagocytes to generate free radicals was determined using zymosan stimulated chemiluminescence (CL). Values were then expressed as peak CL/106 PMN. PMN peak CL fell progressively with time of oxygen exposure. Peak CL by PMN from saline pretreated rats breathing oxygen for 3 days was 80% lower than peak CL by PMN from paired rats pretreated with endotoxin. In addition, complement hemolytic activity was not altered in serum from endotoxin pretreated rats following exposure to > 99% oxygen or air for 65 hours. Depletion of complement in rat s prior to oxygen exposure also failed to provide protection from the pleural edema of oxygen toxicity. These results suggest that endotoxin does alter the ability of alveolar PMN from oxygen breathing rats to release free radicals but does not alter serum complement. a