Strieter R M, Remick D G, Lynch J P, Genord M, Raiford C, Spengler R, Kunkel S L
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0360.
Am J Respir Cell Mol Biol. 1989 Jul;1(1):57-63. doi: 10.1165/ajrcmb/1.1.57.
Human tumor necrosis factor-alpha (TNF), a mononuclear phagocyte (MO)-derived peptide, is increasingly being recognized for its pleomorphic immunologic effects. A number of studies have demonstrated that LPS can induce TNF synthesis, but data examining the production and regulation of TNF in human MO populations are lacking. In this study, we present data demonstrating that alveolar macrophages (AMO) and peripheral blood monocytes (PBM) obtained from 10 normal volunteers display a significant difference in both the production of TNF and their susceptibility to TNF regulation by prostaglandin E2 (PGE2) and dexamethasone (Dex). Adherent populations of PBM and AMO were incubated for 18 h in the presence of either LPS (10 micrograms/ml) alone, PGE2 for 1 h prior to LPS challenge, Dex for 1 h prior to LPS challenge, or control media alone. Cell-free supernatants were examined for TNF bioactivity and cellular TNF mRNA was assessed via in situ hybridization and Northern blot analysis. PGE2 and Dex treatment of PBM suppressed LPS-induced TNF production by 78% and 72%, respectively, while AMO-TNF production was suppressed by only 22% and 33%. The accumulation of TNF mRNA in PBM was reduced 63% by PGE2 and 45% by Dex, as assessed by laser densitometry. Similar studies demonstrated that TNF mRNA accumulation in AMO was reduced 12% and 13% by PGE2 and Dex, respectively. A 1,000-fold increase in PGE2 levels was necessary to induce 50% suppression of the maximal response to AMO as compared to PBM. These data support the notion that human MO derived from different compartments or stages of differentiation exhibit differential responsiveness to immunomodulators.
人肿瘤坏死因子-α（TNF）是一种源自单核吞噬细胞（MO）的肽，其多形性免疫效应日益受到认可。多项研究表明，脂多糖（LPS）可诱导TNF合成，但缺乏关于人类MO群体中TNF产生和调节的数据。在本研究中，我们提供的数据表明，从10名正常志愿者获取的肺泡巨噬细胞（AMO）和外周血单核细胞（PBM）在TNF产生及其对前列腺素E2（PGE2）和地塞米松（Dex）调节TNF的敏感性方面均存在显著差异。将PBM和AMO的贴壁群体分别在单独存在LPS（10微克/毫升）、LPS刺激前1小时加入PGE2、LPS刺激前1小时加入Dex或仅加入对照培养基的条件下孵育18小时。检测无细胞上清液中的TNF生物活性，并通过原位杂交和Northern印迹分析评估细胞TNF mRNA。PGE2和Dex处理PBM可分别将LPS诱导的TNF产生抑制78%和72%，而AMO-TNF产生仅被抑制22%和33%。通过激光密度测定法评估，PGE2使PBM中TNF mRNA的积累减少63%，Dex使其减少45%。类似研究表明，PGE2和Dex分别使AMO中TNF mRNA的积累减少12%和13%。与PBM相比，PGE2水平需增加1000倍才能诱导对AMO最大反应的50%抑制。这些数据支持这样一种观点，即源自不同分化阶段或区室的人类MO对免疫调节剂表现出不同的反应性。
