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.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D002630:Chemotactic Factors / Q000494:pharmacology*; D003182:Complement C5 / Q000032:analysis; D015936:Complement C5a; D004546:Elapid Venoms / Q000494:pharmacology; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology*; D008170:Lung Compliance / Q000187:drug effects; D009504:Neutrophils / Q000473:pathology; D011817:Rabbits; D015054:Zymosan / Q000494:pharmacology
D002630:Chemotactic Factors; D003182:Complement C5; D004546:Elapid Venoms; C016310:cobra venom factor; D015936:Complement C5a; D015054:Zymosan