Soluble and particulate activators of complement and granulomatous pulmonary reactions

In order to test the hypothesis that the histological changes of extrinsic allergic alveolitis result from non-specific activation of the complement cascade we studied pulmonary reactions to equivalent doses of soluble and particulate activators of complement in rats. A single intratracheal instillation of zymosan, a particulate activator of the complement system, produced a florid granulomatous pneumonitis which was maximal at 5 days. This granulomatous reaction did not appear to be associated with the development of hypersensitivity to zymosan. Complement depletion by cobra venom factor did not suppress the granulomatous reaction. Equivalent doses of soluble activators of complement failed to produce any inflammatory changes in the lung. Large doses of immune complex produced an acute, complement dependent, haemorrhagic alveolitis which was maximal at 8 hr and which resolved completely by 48 hr. We conclude that the late granulomatous pulmonary reaction to intra-tracheally administered zymosan is not due to an immune response, or a consequence of direct activation of the alternative pathway of complement, but is of 'foreign body' type. We urge caution in drawing conclusions regarding the pathogenesis of the allergic alveolitides on histological appearances alone.