Neutrophils in acidotic haemodialysed patients have lower intracellular pH and inflamed state

Abstract

The effect of intracellular pH (pHi) on neutrophils has not been clearly defined. We used pre-dialysis neutrophils from three groups of haemodialysis (HD) patients having different levels of pre-dialysis plasma bicarbonate concentrations (PHCO3) and pH values (pre-dialysis PHCO3 of groups A, B and C were consistently<or=21, 21-26 and>or=26 mmol/l [mEq/l], respectively) and neutrophils from age- and sex-matched healthy controls to determine pHi, apoptosis, phagocytosis and oxidative burst reactions in vivo. We also studied, in group A, the effect of metabolic acidosis correction on neutrophil function. Furthermore, we investigated the effect of intracellular acidification on neutrophil functioning in vitro. Neutrophils from the HD patients in group A exhibited significantly lower pHi than those in groups B and C. In addition, group A neutrophils had significantly delayed apoptosis, enhanced phagocytosis and increased oxidative burst reactions compared with those in groups B and C. These alterations in neutrophil function in group A were reduced by correcting metabolic acidosis over a period of 1 month. Moreover, our in vitro studies demonstrated that the pHi of neutrophils is positively correlated with apoptosis and inversely correlated with phagocytosis and oxidative burst reactions. HD patients having low PHCO3 exhibited low neutrophil pHi. This intracellular acidification may contribute to the delayed apoptosis, enhanced phagocytosis and increased oxidative burst reactions observed in these neutrophils compared with neutrophils having normal or higher pHi.