Antibody-induced apoptosis in a human leukemia cell line is energy dependent: thermochemical analysis of cellular metabolism.
The mouse monoclonal anti-BAL antibody induced apoptosis in a pre-B acute lymphocytic leukemia cell line within 2 days of incubation, after being crosslinked by a secondary antibody. The antibody specifically recognized a 37 kDa membrane protein that was expressed on a wide spectrum of normal and malignant cells, but induced programmed cell death in only very few of these cells. In this study, we have followed the initial kinetics of the antibody-induced cell death in the human acute lymphocytic leukemia cell line KM-3, by microcalorimetric measurements in conjunction with determination of the cellular proliferation rate and DNA fragmentation. An increase in metabolic activity was observed already after incubating the cells for 20 min with crosslinked anti-BAL antibody, which was several hours before significant growth inhibition and DNA fragmentation were detected. These data show for the first time that the initiation phase of antibody-induced apoptosis is an active, energy-dependent process and not merely an effect of receptor blocking.
Wallén-Ohman
M
M
Department of Immunotechnology, Lund University, Sweden.
Lönnbro
P
P
Schön
A
A
Borrebaeck
C A
CA
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000276:immunology / Q000378:metabolism*; D002151:Calorimetry; D003432:Cross-Linking Reagents; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000378:metabolism*; D004734:Energy Metabolism; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D010101:Oxygen Consumption; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D007773:Lactates