Antibacterial Host Defense Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Antibacterial Host Defense Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
J Immunol. 2014 Aug 1;193(3):1392-7. doi: 10.4049/jimmunol.1400886. Epub 2014 Jun 27.
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.
富含脂质的巨噬细胞是动脉粥样硬化和结核病等多种疾病的病理学基础。有三种常见的刺激因素被认为可以促进巨噬细胞脂质储存：组织氧分压（pO2）低、细胞外 pH 值（pHO）低以及暴露于细菌 LPS 等激动剂。我们注意到，对低 pO2 或激动剂细菌分子作出反应的细胞通常通过分泌乳酸和其他羧酸来降低 pHO，因此我们研究了 pHO 如何影响低 pO2 和 LPS 对三酰基甘油（TAG）储存的刺激作用。我们发现，当原代巨噬细胞在 21%氧气、4%氧气或在两种氧气浓度下用 LPS 培养时，在 48-72 小时孵育后 TAG 的保留与 pHO 呈反比。将 pHO 维持在~7.4 足以防止由低 pO2 或 LPS 引起的长期 TAG 储存增加。pHO 对 TAG 保留的强烈影响可能解释了为什么富含脂质的巨噬细胞存在于某些组织环境中而不存在于其他组织环境中。也有可能是其他目前归因于低 pO2 或细菌激动剂的长期细胞变化，至少部分是由这些刺激物诱导的 pHO 降低所促进的。
