Calcium-dependent intracellular acidification dominates the pH response to mitogen in human T cells.
The effects of a phorol ester and a mitogenic lectin on the intracellular pH (pHi) of human T lymphocytes was investigated. In contrast to the cytoplasmic alkalinization induced by 12-0-tetradecanoylphorbol-13-acetate, an acidification was recorded in cells treated with phytohemagglutinin. This decrease in pHi was magnified in Na+-free medium or in the presence of amiloride analogues, suggesting that activation of Na+/H+ exchange partially counteracts the phytohemagglutinin-induced acidification. The decrease in pHi was dependent on a sustained increase in cytosolic free Ca2+ and could be mimicked by addition of the divalent cation ionophore, ionomycin. The elevation of cytosolic free Ca2+ leads to metabolic H+ (equivalent) generation with consequent cytoplasmic acidification, which in human T cells predominates over the concurrent activation of the Na+/H+ antiport. These findings argue against the notion that activation of Na+/H+ exchange is a signal for the initiation of proliferation.
Gelfand
E W
EW
Division of Immunology and Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada.
Cheung
R K
RK
Grinstein
S
S
D002118:Calcium / Q000502:physiology*; D003593:Cytoplasm / Q000502:physiology; D004987:Ethers / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015759:Ionomycin; D008213:Lymphocyte Activation / Q000187:drug effects; D008564:Membrane Potentials; D009550:Nigericin / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004987:Ethers; D010835:Phytohemagglutinins; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate; D009550:Nigericin; D002118:Calcium