Altered intracellular pH regulation in neutrophils from patients with cystic fibrosis
2000
Cystic fibrosis (CF) is a condition characterized by neutrophil-mediated lung damage and bacterial colonization. The physiological basis for reported functional alterations in CF neutrophils, including increased release of neutrophil elastase, myeloperoxidase, and oxidants, is unknown. These processes are, however, regulated by intracellular pH (pHi). We demonstrate here that pHi regulation is altered in neutrophils from CF patients. Although resting pHi is similar, pHi after acid loading and activation (N-formyl-methionyl-leucyl-phenylalanine and phorbol 12-myristate 13-acetate) is more acidic in CF cells than in normal cells. Furthermore, patients with non-CF-related bronchiectasis handle acid loading and activation in a fashion similar to subjects with normal neutrophils, suggesting that chronic pulmonary inflammation alone does not explain the difference in pHi. This is further supported by data showing that normal neutrophils exposed to the CF pulmonary milieu respond by increasing pHi as opposed to ...
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