Ethanol inhibits ligand-activated Ca2+ channels in human B lymphocytes.
Ethanol reportedly is immunosuppressive, interfering with lymphocyte proliferation. To investigate the basis for this immunosuppression, the effects of acute treatment with ethanol were studied on Ca2+ mobilization in tonsillar B lymphocytes and the human lymphoblastoid B-cell line, Ramos. The level of intracellular Ca2+ was monitored in cells loaded with the fluorescent dye indo-1 following stimulation with either anti-IgM antibody or platelet activating factor. The effect of ethanol was also examined on the induction of the early proto-oncogene c-fos in these cells. Ethanol inhibited ligand-activated Ca2+ mobilization due to transmembrane influx but not intracellular store release, in a dose- and time-dependent manner. This inhibition was not due to the inability of anti-IgM to bind to its surface receptor nor to membrane depolarization induced by ethanol. Ethanol also inhibited the Ca2(+)-dependent induction by anti-IgM of c-fos in these cells. The inhibitory effects of ethanol on ligand-activated Ca2+ channels and subsequent induction of c-fos may provide the basis for its immunosuppressive action.
Brodie
C
C
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80224.
Domenico
J
J
Mazer
B D
BD
Gelfand
E W
EW
D000888:Antibodies, Anti-Idiotypic; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D006801:Humans; D007075:Immunoglobulin M; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D000090063:Proto-Oncogene Mas
D000888:Antibodies, Anti-Idiotypic; D015220:Calcium Channels; D007075:Immunoglobulin M; C000715470:MAS1 protein, human; D010972:Platelet Activating Factor; D000090063:Proto-Oncogene Mas; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D002118:Calcium