Mediators of lung injury in mice following systemic activation of complement.
Acute lung injury has been produced in mice by the intravenous injection of cobra venom factor. The marked attenuation of lung injury in C5-deficient mice indicates an absolute requirement for C5 in the development of lung injury. Similar studies carried out in beige mice suggest that leukocytic proteinases play, at best, a limited role in the injury. Neutrophil or platelet depletion resulted in a marked reduction in the extent of lung injury, suggesting that both platelets as well as neutrophils contribute to the injury. Treatment of mice with catalase provided a marked degree of protection from the lung injury, while treatment with superoxide dismutase produced limited protection, which suggests that H2O2 or its derivatives are involved in the induction of acute lung injury. By the use of transmission electron microscopy, areas of lung vascular injury, as manifested by extensive blebbing of endothelial cells, were associated with intravascular aggregates of platelets, neutrophils, and fibrin. Finally, lipoxygenase and thromboxane synthetase inhibitors afforded some protection against cobra venom factor-induced acute lung injury, while cyclooxygenase inhibitors gave variable results. These data suggest that acute lung injury in mice following systemic activation of complement has an absolute requirement for C5, is dependent on a role of both neutrophils as well as platelets, and can be linked to the generation of toxic oxygen products by neutrophils.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D003167:Complement Activation; D003182:Complement C5 / Q000172:deficiency / Q000502:physiology; D004546:Elapid Venoms / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D055370:Lung Injury; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology
D003182:Complement C5; D004546:Elapid Venoms; D002374:Catalase; D013482:Superoxide Dismutase