Abstract
Changes in intracellular pH (pHi) and sodium ion (Na+) occur during mitogenic activation of murine lymphocytes. A sodium/hydrogen (Na+/H+) antiport exists in murine lymphocytes and has the potential to regulate both the Na+ and H+ content of lymphocytes. Amiloride (A), an inhibitor of the Na+/H+ antiport, was used to determine if inhibition of Na+/H+ antiport would result in a functional change in human PBM mitogenesis. We studied the effect of (A) on DNA synthesis and immunoglobulin (Ig) production by normal human PBMs activated in vitro by the polyclonal lymphocyte activators, PWM and PHA, and by alloantigen stimulated PBMs (irradiated HIA-DR+ Raji cells). A dose dependent inhibition of (3H)-thymidine incorporation was observed in cells incubated with (A) in concentrations ranging from 1um-100um. Mean reductions of control values in mitogen-activated and allo-antigen-activated cells at 100um of (A) were 40% and 84%, respectively. Production of IgG and IgM determined by an ELISA system was similarity inhibited by (A). (A) was not cytotoxic and did not affect unactivated PBMs. Na+/H+ antiport was demonstrated in cells using dimethylcarboxyfluorescin. In summary: a) Na+/H+ antiport activity exist in human PBMs, is dependent on extracellular Na+ and is (A)-sensitive; b) (A) exerts a dose dependent inhibition of DNA synthesis and Ig production by mitogen and alloantigen activated PBMs; c) (A) may exert its immunosuppressive effect by inhibiting Na+/H+ antiport.
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Jordan, S., Yamaguchi, D., Sakai, R. et al. 992 AMILORIDE SUPPRESSES BLASTOGENESIS AND IMMUNOGLOBU LIN PRODOCTION BY HUMAN PERIPHERAL BLOOD MONONUCLE AR CELLS (PBMs). Pediatr Res 19, 276 (1985). https://doi.org/10.1203/00006450-198504000-01022
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DOI: https://doi.org/10.1203/00006450-198504000-01022