Role of the Complement System in the Acute Respiratory Effects of Inhaled Endotoxin and Cotton Dust

Abstract

Components of the complement system are thought to play a role in the respiratory effects of inhaled organic dusts encountered in occupational settings such as grain storage sites and cotton mills. This hypothesis is based upon observations that grain dusts and endotoxin can activate complement in vitro and in vivo and that the complement system appears to contribute to the endotoxin-induced lung injury of septic shock. The present study examined whether the inflammatory effects of inhaled endotoxin and cotton dust were (1) blocked by decomplementing animals with cobra venom factor (CVF) or (2) present in animals genetically deficient in specific components of the complement system. in untreated and sham-treated guinea pigs, inhaled endotoxin produced significant increases in biochemical and cellular indices of pulmonary injury in bronchoalveolar lavage fluid. Treatment of guinea pigs with 200 units CVF/kg at 24 h prior to exposure did not block the biochemical and cellular changes produced by inhaled endotoxin or cotton dust. Guinea pigs deficient in the fourth component of complement (C4) also demonstrated evidence of pulmonary injury roughly equivalent to that of normal guinea pigs exposed to inhaled endotoxin or cotton dust. Finally, mice genetically deficient in the fifth component of complement (C5) did not exhibit a decreased pulmonary response to inhaled endotoxin compared to C5-sufficient mice. These studies suggest that despite in vitro and in vivo evidence of complement activation by endotoxin and extracts of organic dusts, the complement system may not play a major role in the acute respiratory effects of inhaled endotoxin and cotton dust.