Homologous complement activation on drug-induced apoptotic cells from a human lung adenocarcinoma cell line

Summary Activation of the alternative pathway of homologous complement (C) was observed in a human lung adenocarcinoma cell line, CADO 43, after the cells had become 'apoptotic following treatment in vitro with vincristine and predonisolone. Deposition of C3b and C3bi on the serumtreated apoptotic cells was revealed by flow cytometry with anti-C3b and -C3bi-specific antibodies and immunoblotting with anti-C3 antibody immunoprecipitates extracted from solubilized fractions of serum-treated apoptotic cells. Two molecular mechanisms were found to be responsible for this post-apoptotic C-activation. Firstly, all C regulators, decay accelerating factor (DAF), membrane cofactor protein (MCP) and C3b/C4b receptor (CR1), were diminished on the cell surface concomitantly with the apoptotic process. Secondly, unidentified molecules which potentially activate homologous C and accept C3b/C3bi fragments became expressed on the cell surface during the apoptotic process. These findings may explain the mechanism whereby tumor cells are efficiently eliminated through chemotherapy.