Elevation of cytosolic calcium is sufficient to induce growth inhibition in a B cell lymphoma.
Recently, we have described that anti-IgM antibodies profoundly inhibited the growth of BKS-2, an immature B cell lymphoma. In this report, we demonstrated that ionomycin alone at very low concentrations (20 nM) inhibited the growth of BKS-2 cells completely. The levels of intracellular Ca2+ induced by the inhibitory concentrations of ionomycin were comparable to those in anti-IgM-treated cells. The growth inhibition caused by ionomycin was reversed by phorbol 12-myristate 13-acetate and lipopolysaccharide. In addition, the immunosuppressants, cyclosporin A and FK506 conferred significant protection from the negative signal induced by ionomycin. However, either cyclosporin A, FK506 or lipopolysaccharide was not found to have direct effect on ionomycin-induced Ca2+ mobilization in BKS-2 cells. Also, ionomycin augmented the anti-IgM-induced growth arrest in these cells. Furthermore, BKS-2 cells that were exposed to anti-IgM or ionomycin underwent apoptosis as characterized by DNA fragmentation. Thus, the characteristics of growth inhibition induced by ionomycin and anti-IgM appeared to be similar in that phorbol 12-myristate 13-acetate, lipopolysaccharide, cyclosporin A and FK506 caused significant reversal from such negative signals and both ionomycin and anti-IgM induced apoptosis in these cells. Altogether, these results showed that the elevation of intracellular Ca2+ alone was sufficient to inhibit the growth of some B lymphoma cells.
Muthukkumar
S
S
Department of Microbiology and Immunology, University of Kentucky, Lexington 40536-0230.
Udhayakumar
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V
Bondada
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S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D007075:Immunoglobulin M; D015759:Ionomycin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D016559:Tacrolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D015759:Ionomycin; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016559:Tacrolimus