Extracellular acidic pH modulates oxygen-dependent cytotoxic responses mediated by polymorphonuclear leucocytes and monocytes

Abstract

SUMMARYIn the present study, we compared the ability of human neutrophils and monocytes to display oxygen-dependent cytotoxic responses at pH 7-4 and 6-2. Our results show that cytotoxicity induced by immune complexes (IC), zymosan, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A) were markedly increased when they were carried out at pH 6-2 instead of pH 7-4. Cytotoxicity induced by phorbol myristate acetate (PM A), on the contrary, was significantly decreased at pH 6 2. It is noteworthy that cytotoxic responses induced by IC, zymosan and Con A were also increased when, 2 h after effector cell stimulation at pH 6 2, cytotoxicity was measured at pH 7 4. Finally, when we examined possible mechanisms involved in the augmentation of cytotoxicity, we observed that the oxidative response of IC-stimulated neutrophils, measured as chemiluminescence emission, was not increased at pH 6 2, on the contrary, it was significantly decreased. The relevance of these results is discussed.

Studying Neutrophil Function in vitro: Cell Models and Environmental Factors

“… 189 , 190 In addition, Geffner et al observed an increased cytotoxic capacity of neutrophils under low pH, despite earlier reports of an inhibited respiratory burst in acidic conditions. 191 The authors hypothesize that while the production of some ROS species is inhibited, the production of others may be increased, contributing to neutrophil cytotoxicity; however, more research is needed to test this hypothesis.…”