Neutralization and transfer of lipopolysaccharide by phospholipid transfer protein
Neutralization and transfer of lipopolysaccharide by phospholipid transfer protein
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DOI：
10.1074/jbc.271.21.12172
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发表时间：
1996-05-24
影响因子：
4.8
通讯作者：
Wright, SD
中科院分区：
文献类型：
--
作者：
Hailman, E;Albers, JJ;Wright, SD
磷脂转移蛋白（PLTP）和脂多糖结合蛋白（LBP）是在人血浆中发现的脂质转移蛋白。PLTP与LBP有24%的序列相似性。PLTP介导脂蛋白颗粒之间磷脂的转移和交换，而LBP将细菌脂多糖（LPS）转移到脂蛋白颗粒或CD14（LPS的可溶性和细胞表面受体）。我们询问PLTP是否可以与LPS相互作用并介导LPS转移到脂蛋白或CD14，PLTP能够结合并中和LPS：LPS与纯化的重组PLTP（rPLTP）孵育导致LPS刺激中性粒细胞粘附反应的能力受到抑制，并且向血液中加入rPLTP抑制了响应于LPS的细胞因子产生。采用荧光去猝灭实验和天然凝胶电泳检测rPLTP对LPS的转移。结果表明，rPLTP能够介导LPS在胶束之间的交换以及LPS向重组HDL颗粒的转移，但它不能将LPS转移到CD 14。与这些发现一致，rPLTP不介导中性粒细胞对LPS的CD14依赖性粘附反应。这些结果表明，虽然PLTP和LBP都结合并转移LPS，但PLTP不能将LPS转移至CD14，因此不介导细胞对LPS的应答。
Phospholipid transfer protein (PLTP) and lipopolysaccharide-binding protein (LBP) are lipid transfer proteins found in human plasma. PLTP shares 24% sequence similarity with LBP. PLTP mediates the transfer and exchange of phospholipids between lipoprotein particles, whereas LBP transfers bacterial lipopolysaccharide (LPS) either to lipoprotein particles or to CD14, a soluble and cell-surface receptor for LPS, We asked whether PLTP could interact with LPS and mediate the transfer of LPS to lipoproteins or to CD14, PLTP was able to bind and neutralize LPS: incubation of LPS with purified recombinant PLTP (rPLTP) resulted in the inhibition of the ability of LPS to stimulate adhesive responses of neutrophils, and addition of rPLTP to blood inhibited cytokine production in response to LPS. Transfer of LPS by rPLTP was examined using fluorescence dequenching experiments and native gel electrophoresis. The results suggested that rPLTP was able to mediate the exchange of LPS between micelles and the transfer of LPS to reconstituted HDL particles, but it did not transfer LPS to CD14. Consonant with these findings, rPLTP did not mediate CD14-dependent adhesive responses of neutrophils to LPS. These results suggest that while PLTP and LBP both bind and transfer LPS, PLTP is unable to transfer LPS to CD14 and thus does not mediate responses of cells to LPS.