Modulation of the macrophage respiratory burst by an acidic environment: The critical role of cytoplasmic pH regulation by proton extrusion pumps

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Surgery; (USA)

OSTI ID:6518432

Swallow, C J; Grinstein, S; Sudsbury, R A; Rotstein, O D ^[1]

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1. Toronto General Hospital, Ontario (Canada)

Within the acidic milieu of an abscess or tumor, macrophages must be able to maintain their cytoplasmic pH (pHi) close to the physiologic range to ensure optimal cell function. Our recent studies have demonstrated that a proton-extrusion mechanism with the characteristics of an H+ adenosine triphosphatase mediates pHi recovery in acid-loaded macrophages. These studies were designed to examine the role of these H+ pumps in maintaining cell function in an acidic extracellular environment. Peritoneal macrophages were tested for superoxide production in response to phorbol myristate acetate at either physiologic or acidic extracellular pH (pHo; 7.35 or 6.70, respectively). pHi was measured with the fluorescent dye 2',7'-biscarboxy-ethyl-5(6)-carboxy-fluorescein. Bafilomycin A1, a specific H+ adenosine triphosphatase inhibitor, was used to examine the contribution of the H+ pump to pHi regulation and cell function. At pHo 7.35, bafilomycin A1 had no effect on pHi or phorbol myristate acetate-stimulated superoxide production. However, at pHo 6.70, bafilomycin A1 reduced pHi to 6.61 +/- 0.01 versus 6.79 +/- 0.01 in control cells (p less than 0.001) and caused a concomitant reduction in superoxide production to 4.8 +/- 1.2 versus 13.0 +/- 1.2 nmol/10(6) cells/40 min in control cells (p less than 0.001). To determine whether the observed reduction in superoxide formation was the result of the pHi reduction, superoxide production was measured in cells whose pHi was pharmacologically clamped at various levels according to the K+/nigericin method. Lowering pHi from 6.80 to 6.60 caused a significant reduction in superoxide production from 13.1 +/- 1.8 to 7.5 +/- 0.9 nmol/10(6) cells/40 min (p less than 0.01). Thus H+ extrusion pumps are important to maintenance of macrophage pHi at low pHo, permitting continued superoxide production under these conditions.

• OSTI ID: 6518432
• Journal Information: Surgery; (USA), Vol. 108:2; ISSN 0039-6060
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PROTONS
MEMBRANE TRANSPORT
SUPEROXIDE RADICALS
BIOSYNTHESIS
ANTIBIOTICS
ATP
CYTOPLASM
ENZYME INHIBITORS
EXTRACELLULAR SPACE
FLUORESCEIN
MACROPHAGES
PERITONEUM
PH VALUE
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
AROMATICS
BARYONS
CARBOXYLIC ACIDS
CARCINOGENS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DRUGS
DYES
ELEMENTARY PARTICLES
ESTERS
FERMIONS
HADRONS
HYDROXY ACIDS
HYDROXY COMPOUNDS
MEMBRANES
NUCLEONS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHAGOCYTES
PHENOLS
POLYPHENOLS
RADICALS
SEROUS MEMBRANES
SOMATIC CELLS
SPACE
SYNTHESIS
560300* - Chemicals Metabolism & Toxicology