ABSENCE OF INFLAMMATORY LUNG INJURY IN RABBITS CHALLENGED INTRA-VASCULARLY WITH COMPLEMENT-DERIVED CHEMOTACTIC FACTORS

Abstract

Systemic activation of the complement system results in the generation of chemotactic factors that were suggested to play a role in the pathogenesis of inflammatory pulmonary diseases such as the adult respiratory distress syndrome. 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 was questioned. As had been described previously for CVF and ZAP, i.v. administered rabbit C5a also caused an acute neutropenia along with sequestration of neutrophils within the pulmonary vasculature. No significant lung inflammation as measured by neutrophil emigration or increased vascular permeability occurred with any 1 of the 3 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. 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. Complement activation, as an isolated event, may be an insufficient insult in the lung to produce significant lung injury.