Absence of inflammatory lung injury in rabbits challenged intravascularly with complement-derived chemotactic factors.

Systemic activation of the complement system results in the generation of chemotactic factors that have been suggested to play a role in the pathogenesis of inflammatory pulmonary diseases such as the adult respiratory distress syndrome. This led us to ask whether systemic complement activation by cobra venom factor (CVF) or intravascularly administered zymosan-activated rabbit plasma (ZAP) or rabbit C5a would result in lung injury. As had been described previously for CVF and ZAP, intravenously administered rabbit C5a also caused an acute neutropenia along with sequestration of neutrophils within the pulmonary vasculature. However, no significant lung inflammation as measured by neutrophil emigration or increased vascular permeability occurred with any of the three stimuli. Only when these agents were combined with anesthesia, surgical manipulation, and intubation did significant neutrophil emigration into alveoli occur, but again without any change in vascular permeability. After administration of ZAP, a decrease in dynamic compliance and an increase in pulmonary resistance as well as a transient period of hypoxemia occurred that was not observed after CVF or rabbit C5a treatment. Thus, our studies suggest that changes in lung function after ZAP instillation may not represent changes from complement activation alone in that they are not reproduced with CVF or rabbit C5a. We conclude that complement activation, as an isolated event, may be an insufficient insult in the lung to produce significant lung injury.

Pulmonary microvascular alterations and injury induced by complement fragments: synergistic effect of complement activation, neutrophil sequestration, and prostaglandins.

Fragments of C5 that are generated at, or administered to, extravascular sites in the pulmonary parenchyma induced neutrophil infiltration, edema, tissue damage, and a complete inflammatory response. Generation of C5 fragments within the vascular system induced leukocyte sequestration in the pulmonary vasculature, but without detectable increased vascular permeability or neutrophil migration. By contrast, the combination of short episode of hypoxemia with the intravascular C5 activation led significant increases in pulmonary vascular permeability, mild endothelial alterations, and emigration of neutrophils. Infusion of 10 micrograms PGE2 into animals in which intravascular complement had been activated produced changes in the lungs that were similar to, though less severe than, the combination of hypoxia and complement activation.