West M A, Manthei R, Bubrick M P
Hennepin County Medical Center, Division of Surgical Infectious Disease, Minneapolis, Minnesota 55415.
J Trauma. 1993 Apr;34(4):473-9; discussion 479-80. doi: 10.1097/00005373-199304000-00001.
Endotoxin (LPS)-stimulated macrophages release mediators, such as tumor necrosis factor (TNF) and prostaglandin E2 (PGE2), which modulate the function of many different cells. We hypothesize that macrophage regulation is altered in sepsis and that mediators from LPS-stimulated macrophages "autoregulate" their activation state. Alterations in the LPS dose response relationships for inhibition of hepatocyte protein synthesis by hepatic macrophages (hMøs) were examined to investigate factors that regulate hMø activation. In vitro pretreatment was compared using TNF alpha, PGE2, subactivating concentrations of LPS, or LPS plus indomethacin. Pre-exposure to LPS resulted in a dose-dependent loss of subsequent LPS-triggered activation of hMøs in co-culture. Pretreatment with LPS and 1 mumol/L indomethacin partially restored hMø responsiveness. Pre-exposure to PGE2 significantly decreased LPS responsiveness of co-cultured hMøs, suggesting that PGE2 produced by LPS-stimulated hMøs may mediate this effect. Pretreatment of hMøs with TNF alpha, but not IL-1 beta, significantly lowered the LPS concentration required for maximal hMø activation. We conclude that both macrophage mediators and LPS pretreatment alter macrophage activation state. These data suggest an "autoregulatory" role for mediators of LPS-stimulated macrophages in sepsis.
内毒素（脂多糖，LPS）刺激的巨噬细胞会释放介质，如肿瘤坏死因子（TNF）和前列腺素E2（PGE2），这些介质可调节许多不同细胞的功能。我们假设在脓毒症中巨噬细胞调节发生改变，并且来自LPS刺激的巨噬细胞的介质会“自动调节”其激活状态。研究了肝巨噬细胞（hMø）抑制肝细胞蛋白质合成的LPS剂量反应关系的改变，以探究调节hMø激活的因素。使用TNFα、PGE2、亚激活浓度的LPS或LPS加吲哚美辛进行体外预处理并比较。预先暴露于LPS会导致共培养中随后LPS触发的hMø激活呈剂量依赖性丧失。用LPS和1μmol/L吲哚美辛预处理可部分恢复hMø反应性。预先暴露于PGE2会显著降低共培养的hMø对LPS的反应性，表明LPS刺激的hMø产生的PGE2可能介导了这种效应。用TNFα而非IL-1β预处理hMø会显著降低最大程度激活hMø所需的LPS浓度。我们得出结论，巨噬细胞介质和LPS预处理都会改变巨噬细胞激活状态。这些数据表明LPS刺激的巨噬细胞的介质在脓毒症中具有“自动调节”作用。
