Ca2+ influx initiates death of hepatocytes injured by activation of complement.
To clarify the role of cytosolic Ca2+ in hepatocellular death, we exposed cultured hepatocytes to human serum and a monoclonal antibody directed against rat liver plasma membranes to produce complement-mediated cell injury. The change in cytosolic Ca2+ concentration was measured by fura2 and fluo3 fluorescence. With the addition of monoclonal antibody, an increase in cytosolic Ca2+ was observed, followed by cell death. Both the increase in intracellular Ca2+ and cell death were prevented by intracellular Ca2+ chelation or removal of extracellular Ca2+. We conclude that an increase in cytosolic Ca2+ plays a major role in hepatocellular injury induced by exposure of the cell membrane to monoclonal antibody.
First Dept. Of Internal Medicine, Okayama University Medical School, Japan.
Y
Y
Nishikawa
M
M
Ukida
R
R
Matsuo
N
N
Omori
T
T
Tsuji
D000818:Animals; D000911:Antibodies, Monoclonal; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003167:Complement Activation; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D002614:Chelating Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D002118:Calcium