Key role of complement activation and platelet-activating factor in exudate formation in zymosan-induced rat pleurisy

Involvement of complement and platelet-activating factor (PAF) in zymosan-induced rat pleurisy was examined. Only a very low level of complement remained in the exudate at 1-5 hr after zymosan injection, indicating that complement activation had occurred during this period in the pleural cavity. When rats were injected with cobra venom factor (CVF) 24 hr prior to the zymosan injection to deplete complement, the exudate volumes at 0.5 and 5 hr after zymosan injection were significantly reduced. Furthermore, combined treatment with CVF and CV-6209, an antagonist of PAF, also significantly suppressed the exudation but to no further extent than the suppression by CVF alone, suggesting that the level of complement depletion achieved was sufficient to halt PAF synthesis/release. To see if complement activation is involved in PAF production, we examined the PAF production by resident leukocytes in response to zymosan in vitro. When pleural leukocytes were stimulated with zymosan in the presence of rat serum, PAF-like activity both in the medium and in the cellular fraction increased. If the serum was heat inactivated, no PAF-like activity was detected. These results suggest that initial activation of the complement system may occur in the pleural cavity by zymosan and that the activated complement may then stimulate the production of PAF, which in turn elicits the exudate.