Two functionally independent pathways for lipopolysaccharide-dependent activation of mouse peritoneal macrophages.
Two functionally independent pathways for lipopolysaccharide-dependent activation of mouse peritoneal macrophages.
复制标题
DOI：
10.4049/jimmunol.159.10.5079
复制
发表时间：
1997-11
影响因子：
4.4
通讯作者：
C. Amura;L. C. Chen;N. Hirohashi;M. Lei;D. Morrison
中科院分区：
文献类型：
--
作者：
C. Amura;L. C. Chen;N. Hirohashi;M. Lei;D. Morrison
我们研究了人 LPS 结合蛋白 (LBP) 和人杀菌/通透性增加蛋白 (BPI) 对体外 LPS 依赖性激活小鼠硫代乙醇酸盐诱导的腹膜巨噬细胞的影响，并与人 PBMC 进行比较。证实了先前发表的研究，BPI 抑制 LPS 刺激 PBMC 产生细胞因子 TNF-α 和 IL-6 的能力，而 LBP 则增强这种能力。与这些结果形成鲜明对比的是，在相同的体外培养条件下，LBP 和 BPI 均以剂量依赖性方式抑制 LPS 刺激小鼠巨噬细胞产生细胞因子的能力。此外，虽然人BPI也抑制小鼠巨噬细胞中LPS依赖性NO分泌，但人LBP在抑制TNF-α分泌的条件下对NO分泌没有抑制作用。这些数据提供了第一个直接证据，表明小鼠巨噬细胞可能利用两条独立的途径响应脂多糖，从而导致不同的表型反应。
We have investigated the effects of human LPS-binding protein (LBP) and human bactericidal/permeability-increasing protein (BPI) on LPS-dependent activation of mouse thioglycolate-elicited peritoneal macrophages in vitro, in comparison with human PBMCs. Confirming earlier published studies, BPI inhibited, and LBP enhanced, the ability of LPS to stimulate PBMC production of the cytokines TNF-alpha and IL-6. In marked contrast to these results, under identical conditions of in vitro culture, both LBP and BPI suppressed, in a dose-dependent manner, the ability of LPS to stimulate cytokine production in mouse macrophages. Further, while human BPI also suppressed LPS-dependent NO secretion in mouse macrophages, human LBP had no inhibitory effect on NO secretion under conditions that inhibited TNF-alpha secretion. These data provide the first direct evidence that mouse macrophages may utilize two independent pathways in response to LPS, thus leading to different phenotypic responses.