LIPOPOLYSACCHARIDE ACTIVATION OF HUMAN ENDOTHELIAL AND EPITHELIAL-CELLS IS MEDIATED BY LIPOPOLYSACCHARIDE-BINDING PROTEIN AND SOLUBLE CD14

LIPOPOLYSACCHARIDE ACTIVATION OF HUMAN ENDOTHELIAL AND EPITHELIAL-CELLS IS MEDIATED BY LIPOPOLYSACCHARIDE-BINDING PROTEIN AND SOLUBLE CD14
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DOI:
10.1073/pnas.90.7.2744
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发表时间:
1993-04-01
影响因子:
11.1
通讯作者:
TOBIAS, PS
TOBIAS, PS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
PUGIN, J;SCHURERMALY, CC;TOBIAS, PS

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脂多糖(LPS)激活骨髓细胞涉及两种蛋白质,血浆LPS结合蛋白(LBP)和细胞膜CD 14。由甘油磷脂酰肌醇尾部锚定的细胞膜CD 14是LPS-LBP复合物的细胞受体。另一种形式的CD 14,没有脂质尾,作为可溶性血浆蛋白循环。在这项工作中,我们表明,可溶性CD 14(sCD 14)是所需的激活内皮细胞和上皮细胞的LPS。我们提出LPS-LBP复合物将LPS转移到sCD 14,然后LPS-sCD 14复合物与细胞受体结合。对该途径的支持来自于正常人血清中的LBP和CD 14被特异性抗体阻断的实验、血清被纯化的LBP和sCD 14替代的实验以及[H-3]LPS与上皮细胞的特异性结合被定量的实验。
Myeloid cell activation by lipopolysaccharides (LPS) involves two proteins, plasma LPS-binding protein (LBP) and cell-membrane CD14. Cell membrane CD14, anchored by a glycerophosphatidylinositol tail, is the cellular receptor for LPS-LBP complexes. Another form of CD14, without the lipid tail, circulates as a soluble plasma protein. In this work we show that soluble CD14 (sCD14) is required for activation of endothelial and epithelial cells by LPS. We propose that LPS-LBP complexes transfer LPS to sCD14, and the LPS-sCD14 complexes then bind to a cellular receptor. Support for this pathway comes from experiments in which LBP and CD14 in normal human serum are blocked by specific antibodies, experiments in which serum is replaced by purified LBP and sCD14, and experiments in which specific binding of [H-3]LPS to epithelial cells is quantitated.