Activation of the Na+/H+ antiport is not required for lectin-induced proliferation of human T lymphocytes

G. B. Mills, R. K. Cheung, E. J. Cragoe, S. Grinstein, E. W. Gelfand

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Interaction of some mitogenic lectins and growth factors with the cell surface leads to activation of the Na+/H+ antiport and a resultant cytoplasmic alkalinization. Because amiloride inhibits both Na+/H+ exchange and cell proliferation, it has been hypothesized that activation of the antiport is an obligatory requirement and may, perhaps, be the 'trigger' for proliferation. However, concentrations of amiloride which inhibit the antiport also inhibit several other intracellular processes, including protein synthesis and phosphorylation. To determine whether activation of the Na+/H+ antiport is necessary for lectin-induced proliferation, we examined the inhibitory activity of a series of potent amiloride analogs by measuring [3H]thymidine incorporation, cell cycle progression, and induction of the interleukin 2 (IL 2) receptor on human lymphocytes. In medium containing bicarbonate, and at concentrations at least 10 times higher than required to inhibit the antiport, these drugs did not inhibit the proliferative response of human peripheral blood T cells to the mitogen phytohemagglutinin. The amiloride analogs also failed to inhibit induction of the IL 2 receptor. Similarly, with human thymocytes, the amiloride analogs did not inhibit the co-mitogenic effects of the lectins phytohemagglutinin and concanavalin A together with IL 2 or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. This finding suggests that Na+/H+ exchange through the antiport is not an obligatory requirement for activation or proliferation of human lymphocytes or thymocytes.

Original languageEnglish (US)
Pages (from-to)1150-1154
Number of pages5
JournalJournal of Immunology
Volume136
Issue number4
StatePublished - May 14 1986
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Mills, G. B., Cheung, R. K., Cragoe, E. J., Grinstein, S., & Gelfand, E. W. (1986). Activation of the Na+/H+ antiport is not required for lectin-induced proliferation of human T lymphocytes. Journal of Immunology, 136(4), 1150-1154.