Homologous complement activation on drug-induced apoptotic cells from a human lung adenocarcinoma cell line.
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 serum-treated 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.
Hara
T
T
Department of Immunology and Cell Biology, Center for Adult Diseases Osaka, Japan.
Matsumoto
M
M
Tsuji
S
S
Nagasawa
S
S
Hiraoka
A
A
Masaoka
T
T
Kodama
K
K
Horai
T
T
Sakuma
T
T
Seya
T
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D002945:Cisplatin / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014748:Vinca Alkaloids / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D014748:Vinca Alkaloids; D014750:Vincristine; C053989:nedaplatin; D011239:Prednisolone; D002945:Cisplatin