title: Prolonged triglyceride storage in macrophages: pHo trumps pO2 and TLR4.
abstract: Lipid-laden macrophages contribute to pathologies as diverse as atherosclerosis and tuberculosis. Three common stimuli are known to promote macrophage lipid storage: low tissue oxygen tension (pO2), low extracellular pH (pHo), and exposure to agonists such as bacterial LPS. Noting that cells responding to low pO2 or agonistic bacterial molecules often decrease pHo by secreting lactic and other carboxylic acids, we studied how pHo influences the stimulation of triacylglycerol (TAG) storage by low pO2 and LPS. We found that TAG retention after incubation for 48-72 h was inversely related to pHo when primary macrophages were cultured in 21% oxygen, 4% oxygen, or with LPS at either oxygen concentration. Maintaining pHo at ~7.4 was sufficient to prevent the increase in prolonged TAG storage induced by either low pO2 or LPS. The strong influence of pHo on TAG retention may explain why lipid-laden macrophages are found in some tissue environments and not in others. It is also possible that other long-term cellular changes currently attributed to low pO2 or bacterial agonists may be promoted, at least in part, by the decrease in pHo that these stimuli induce.
authors: Antibacterial Host Defense Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors: Mingfang
authors: M
authors: Lu
authors: Antibacterial Host Defense Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors: Terry
authors: T
authors: Kho
authors: Antibacterial Host Defense Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 munfordrs@niaid.nih.gov.
authors: Robert S
authors: RS
authors: Munford
mesh_terms: D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis / Q000276:immunology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption / Q000276:immunology*; D061251:Primary Cell Culture; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism*; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D000217:Acyltransferases
chemical_list: D002264:Carboxylic Acids; D003066:Coenzyme A Ligases; D051048:Diacylglycerol O-Acyltransferase; D005227:Fatty Acids; D008049:Lipase; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014280:Triglycerides; C493487:Tlr4 protein, mouse; C082161:lipopolysaccharide A; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases; C544400:ACSL1 protein, mouse