Abnormal activation of H+ conductance in NADPH oxidase-defective neutrophils.

AUTOR(ES)

Nanda, A

RESUMO

To combat bacterial infection, phagocytes generate superoxide (O2-) and other microbicidal oxygen radicals. NADPH oxidase, the enzyme responsible for O2- synthesis, is deficient in chronic granulomatous disease (CGD) patients. Although O2- generation is accompanied by a large burst of metabolic acid production, intracellular pH (pHi) remains near neutrality due to the concomitant stimulation of H+ extrusion. Three major pathways contribute to pHi regulation in activated phagocytes: Na+/H+ exchange, vacuolar-type H+ pumps, and a H+ conductance. The present study analyzed the relationship between activation of the NADPH oxidase and stimulation of the H+ extrusion mechanisms in human blood neutrophils. Phorbol ester-induced activation of Na+/H+ exchange and H+ pumping occurred normally in cells from CGD patients. Unlike normal individuals, however, CGD patients were unable to activate the H+ conductive pathway. Thus, activation of the H+ conductance appears to be contingent on the assembly of a functional NADPH oxidase. These findings imply a dual role of the NADPH oxidase in O2- synthesis and in the regulation of pHi. The oxidase (or some components thereof) may itself undertake H+ translocation or, alternatively, may signal the activation of a separate H+ conducting entity.

Documentos Relacionados

• Protein kinase C activates an H+ (equivalent) conductance in the plasma membrane of human neutrophils.
• Activation of H+ conductance in neutrophils requires assembly of components of the respiratory burst oxidase but not its redox function.
• Simultaneous activation of NADPH oxidase-related proton and electron currents in human neutrophils
• NAD(P)H oxidase activity in human neutrophils stimulated by phorbol myristate acetate.
• Membrane H+ conductance of Streptococcus lactis.