Intracellular pH regulation in leukocytes: Mechanisms and functional significance

The regulation of the intracellular pH (pH_i) of phagocytic cells is critical to their function and viability. The acidic nature of the abscesses to which these cells migrate and the burden of acid that they generate in the activated state tend to perturb the pH_i outside of the physiological range. Failure to maintain pH_i homeostasis results in decreased cellular enzyme activity, cellular migration, and microbicidal function. Several pH_i regulatory mechanisms, including the sodium-proton exchanger, proton conductive pathways, and a vacuolar type H⁺-ATPase exist in leukocytes and play an important role in preventing deviations in the pH_i away from the physiological range. The last of these mechanisms is central to the regulation of cytoplasmic pH, and is modulated by mediator molecules in the inflammatory mileu.