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Cytoplasmic pH regulation in phorbol ester-activated human neutrophils

Journal Article · · Am. J. Physiol.; (United States)
OSTI ID:6935945
;
Activation of neutrophils by 12-O-tetradecanoylphorbol-13-acetate (TPA) is accompanied by an initial cytoplasmic acidification, followed by an alkalinizing phase due to Na/sup +/-H/sup +/ countertransport. The source of the acidification, which is fully expressed by activation with TPA in Na/sup +/-free or amiloride-containing media, was investigated. The acidification phase was detected also in degranulated and enucleated cytoplasts, ruling out a major contribution by the nucleus or secretory vesicles. Cytoplasmic acidification was found to be associated with an extracellular acidification, suggesting metabolic generation of H/sup +/. Two principal metabolic pathways are stimulated in activated neutrophils; the reduction of O/sub 2/ by NADPH-oxidase and the hexose monophosphate shunt. A good correlation was found between the activity of these pathways and the changes in cytoplasmic pH. Inhibition of superoxide synthesis prevented the TPA-induced cytoplasmic acidification. Moreover, activation of the hexose monophosphate shunt with permeable NADPH-oxidizing agents (in the absence of TPA) also produced a cytoplasmic acidification. The results suggest that the cytoplasmic acidification induced by phorbol esters in neutrophils reflects accumulation of H/sup +/ liberated during the metabolic burst that follows activation.
Research Organization:
Univ. of Toronto, Ontario (Canada)
OSTI ID:
6935945
Journal Information:
Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 251:1; ISSN AJPHA
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL COMPOUNDS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CATIONS
CHARGED PARTICLES
CHEMICAL ACTIVATION
ESTERS
HYDROGEN IONS
HYDROGEN IONS 1 PLUS
IONS
LEUKOCYTES
MATERIALS
MEMBRANE TRANSPORT
NEUTROPHILS
ORGANIC COMPOUNDS
PH VALUE
PHORBOL ESTERS
SODIUM COMPOUNDS