The possibility of direct inactivation of C3 by granular enzymes from polymorphonuclear leukocytes(PMNLs) in pleural empyema was examined. As a group, pleural empyema from 10 patients with purulent effusions and a positive bacteriologic culture cleaved significantly more 125I-labeled C3 bound to Sepharose (18.4% ± 7.3%) than did 19sterile pleural effusions (2.4% ± 0.9%; P << 0.001)and sonicates from bacterial strains commonly found in empyema (1.4% ± 0.2%). Granular enzymesfrom 7 × 106 PMNLs cleaved 78.5% of 125I-labeled C3 bound to Sepharose. When proteolysis of 125I-labeled C3 after incubation with pleural empyema or PMNL granular enzymes was examined with polyacrylamide gel electrophoresis, breakdown products were similar. Granulocyte elastase-like activity was detected in four samples of pleural empyema. Granulocyte elastase inhibitors, as well as 10% human serum, effectively suppressed cleavage of C3 and elastase-like activity. In pleural empyemas, granular enzymes from PMNLs, especially elastase, apparently contribute to low complement-mediated opsonic activity by direct inactivation of C
