Heming T A, Davé S K, Tuazon D M, Chopra A K, Peterson J W, Bidani A
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-0876, U.S.A.
Clin Sci (Lond). 2001 Sep;101(3):267-74.
Cellular acid-base status has been found to exert selective actions on the effector functions of activated macrophages (mphi). We examined the effects of extracellular pH (pH(o)) on the production of tumour necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS) in resident alveolar mphi. Cells were obtained by bronchoalveolar lavage of rabbits, activated in vitro with LPS, and cultured at pH(o) 5.5, 6.5 or 7.4 for up to 18 h. The relative abundance of TNF-alpha mRNA peaked at approximately 2 h. The peak transcript abundance was increased at lower pH(o) values. This finding probably reflected pre-transcription/transcription effects of pH, in as much as the stability of TNF-alpha mRNA induced with phorbol ester was unaffected by the experimental pH(o) values. TNF-alpha secretion by LPS-treated mphi decreased at lower pH(o) values. The TNF-alpha content of mphi-conditioned media decreased progressively with decrements in pH(o). The reduced TNF-alpha secretion at pH(o) 5.5 was accompanied by an increase in the cytosolic TNF-alpha content (compared with that at pH(o) 7.4), indicating that pH(o) altered TNF-alpha secretion due, in part, to the intracellular retention of synthesized cytokine (i.e. a post-translation effect). The data show that pH(o) has multiple effects (pre-transcription/transcription and post-translation) on TNF-alpha production induced by LPS in resident alveolar mphi. These results suggest that the role of alveolar mphi in inflammatory responses is modulated by pH(o), which may be important in tumours/abscesses and sites of infection where the external milieu is acidic.
已发现细胞酸碱状态对活化巨噬细胞（mphi）的效应功能具有选择性作用。我们研究了细胞外pH值（pH(o)）对驻留肺泡mphi中脂多糖（LPS）诱导的肿瘤坏死因子-α（TNF-α）产生的影响。通过对兔进行支气管肺泡灌洗获得细胞，在体外用LPS激活，并在pH(o) 5.5、6.5或7.4下培养长达18小时。TNF-α mRNA的相对丰度在约2小时达到峰值。在较低的pH(o)值下，峰值转录本丰度增加。这一发现可能反映了pH的转录前/转录效应，因为佛波酯诱导的TNF-α mRNA的稳定性不受实验pH(o)值的影响。LPS处理的mphi分泌的TNF-α在较低的pH(o)值下减少。mphi条件培养基中的TNF-α含量随着pH(o)的降低而逐渐减少。在pH(o) 5.5时TNF-α分泌减少伴随着细胞溶质TNF-α含量的增加（与pH(o) 7.4时相比），表明pH(o)改变TNF-α分泌部分是由于合成的细胞因子在细胞内滞留（即翻译后效应）。数据表明pH(o)对驻留肺泡mphi中LPS诱导的TNF-α产生具有多种作用（转录前/转录和翻译后）。这些结果表明肺泡mphi在炎症反应中的作用受到pH(o)的调节，这在外部环境呈酸性的肿瘤/脓肿和感染部位可能很重要。
