Human macrophages respond to LPS in a serum-independent, CD14-dependent manner
Human macrophages respond to LPS in a serum-independent, CD14-dependent manner
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DOI：
10.1016/s0165-2478(96)02645-4
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发表时间：
1996-12-01
影响因子：
4.4
通讯作者：
Eperon, S
中科院分区：
文献类型：
--
作者：
Jungi, TW;Brcic, M;Eperon, S
脂多糖（LPS）激活单核细胞的两个关键介质是急性期血浆因子、脂多糖结合蛋白（LBP）和细胞表面表达的CD 14。巨噬细胞（M phi）是否以类似的方式识别和响应LPS尚不清楚。在这里，我们表明，人单核细胞衍生的M phi响应LPS的肿瘤坏死因子-α的释放和促凝活性上调，在血清的存在或不存在下，通过类似的剂量反应曲线：这表明体液因素，如LBP是相对不重要的M phi的激活。LPS对M phi的血清依赖性和非血清依赖性激活都需要细胞CD 14，这一点通过CD 14特异性抗体阻断研究得到证实。从单核细胞样细胞系Mono Mac-6选择高LPS敏感性的克隆显示出类似的特性。当不含血清洗涤并在骨化三醇存在下培养时，无论是否存在血清，它们都以类似的方式对LPS作出反应，并且这种反应被抗CD 14抑制。据推测，在其分化过程中，M phi获得血清因子LBP的功能替代物，从而能够在LBP浓度低的环境中识别低LPS浓度。确定这是否是高亲和力LBP受体、LBP本身或另一种细胞表面成分将是有意义的。版权所有（C）1996 Elsevier Science B. V.
Two crucial mediators of monocyte activation by lipopolysaccharide (LPS) are the acute phase plasma factor, lipopolysaccharide binding protein (LBP) and cell-surface-expressed CD14. Whether macrophage (M phi) recognize and respond to LPS in a similar manner is unknown. Here we show that human monocyte-derived M phi respond to LPS by tumor necrosis factor-alpha release and procoagulant activity upregulation by a similar dose response curve in the presence or absence of serum: suggesting that humoral factors such as LBP are relatively unimportant in the activation of M phi. Both serum-dependent and serum-independent activation of M phi by LPS require cellular CD14, as evidenced by blocking studies with CD14-specific antibodies. Clones from the monocytoid cell line Mono Mac-6 selected for high LPS sensitivity displayed similar properties. When washed free of serum and cultured in the presence of calcitriol, they responded to LPS in a similar manner, regardless of the presence or absence of serum, and this response was inhibited by anti-CD14. It is hypothesized that during their differentiation, M phi acquire a functional substitute for the serum factor LBP, thereby being able to recognize low LPS concentrations in a milieu low in LBP concentration. It will be of interest to determine whether this is a high-affinity LBP receptor, LBP itself, or another cell surface constituent. Copyright (C) 1996 Elsevier Science B.V.