Delineation of the Role of a Na+/Ca2+ Exchanger in Regulating Intracellular Ca2+ in T Cells

Autor: Edward J. Cragoe, Mary C. Wacholtz, Peter E. Lipsky
Rok vydání: 1993
Předmět:
Zdroj: Cellular Immunology. 147:95-109
ISSN: 0008-8749
Popis: One of the metabolic events that results from ligation of the CD3-TCR is an increase in [Ca2+]i. The mechanisms that generate this rise in [Ca2+]i are poorly understood, but involve mobilization of intracellular Ca2+ stores and the movement of extracellular Ca2+ into the cell. To examine the role of Na+/Ca2+ exchange in the increase in [Ca2+]i after CD3-TCR engagement, the effects of specific inhibitors of Na+/Ca2+ exchange, DCB, CBDMB, and bepridil, were examined. Inhibitors of Na+/Ca2+ exchange suppressed IL2 production and the rise in [Ca2+]i in Jurkat cells stimulated by anti-CD3 mAb. Mobilization of intracellular Ca2+ stores and mitogen-stimulated inositol phosphate production were not inhibited by these agents. Inhibitors of Na+/Ca2+ exchange also inhibited mitogen responses of normal T cells and the sustained increase in [Ca2+]i resulting from cross-linking class I MHC molecules, addition of PHA, or anti-CD3 mAb. Additional evidence for an important role of a Na+/Ca2+ exchanger in generating increases in [Ca2+]i after CD3 ligation was the finding that replacing extracellular Na+ with Li+, that cannot be transported by the Na+/Ca2+ exchanger, nearly abrogated the rise in [Ca2+]i induced by cross-linking CD3. These results are consistent with the conclusion that a Na+/Ca2+ exchanger is important in regulating changes in [Ca2+]i that are critical for T cell activation.
Databáze: OpenAIRE