Lactate transport in macrophages.
Macrophages perform phagocytic and effector activities in a number of different tissues. The environment of the inflammatory foci in which they function is often acidic and contains an abundance of lactate. We characterized the ability of thioglycollate-elicited mouse peritoneal macrophages to accumulate lactate from the medium and to use this lactate to maintain intracellular energy stores. Lactate uptake was stereospecific for L-lactate and was inhibited by the organic anion transport blocker probenecid but not by concentrations of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid that block anion exchangers. L-[14C]Lactate uptake was not affected by variation of the extracellular Na+ concentration but was enhanced by acidification of the extracellular medium, suggesting that lactate uptake was mediated by a proton cotransport system. The enhanced accumulation of [14C]-lactate seen in medium at pH 6.0 to 6.5 was inhibited by probenecid or by an excess of unlabeled L-lactate. When macrophages were incubated in PBS without glucose for 6 h, intracellular stores of phosphocreatine were 13 nmol/mg of protein, compared with 44 nmol/mg of protein in cells incubated in medium containing glucose. When lactate was substituted for glucose, phosphocreatine stores were 32 nmol/mg of protein. These studies reveal that macrophages take up L-lactate in a pH-dependent manner and that lactate uptake occurs via a probenecid-inhibitable monocarboxylate transporter; they suggest that macrophages can utilize this lactate as an energy source.
Loike
J D
JD
Rover Physiology Laboratories, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Kaback
E
E
Silverstein
S C
SC
Steinberg
T H
TH
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008985:Monensin / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D012964:Sodium / Q000378:metabolism; D013237:Stereoisomerism
D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D008985:Monensin; D012964:Sodium; D009550:Nigericin