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.