Leukotriene D 4 ‐induced increases in the cytoplasmic pH of human myelocytic leukocytes

The effects of leukotriene D 4 on the intracellular pH of human myelocytes, derived from cultured HL‐60 cells by dimethylsulfoxide‐induced differentiation, were quantified with the fluorescent indicator 2′,7′‐bis‐(2‐carboxy‐ethyl)‐5,6‐carboxyfluorescein. Leukotriene D 4 , but not C 4 or E 4 , increased intracellular pH optimally by 3 min with a half‐maximal effect at 1–2 nM. The increases in intracellular pH stimulated by leukotriene D 4 were prevented by pretreatment of myelocytes with leukotriene D 4 but not peptide chemotactic factors. Analogs of amiloride that inhibit selectively the Na + /H + antiport also prevented the intracellular alkalinization induced by leukotriene D 4 . The rate of recovery of intracellular pH after an acid load with 30 mM sodium propionate was approximately 30% higher at each level of intracellular pH for myelocytes exposed to leukotriene D 4 than for those challenged in buffer alone. The increase elicited by leukotriene D 4 in the adherence of myelocytic leukocytes to surfaces thus is associated with an enhanced sensitivity of the Na + /H + antiport to intracellular pH, that is, not coupled to an earlier rise in the cytosolic level of Ca +2 .