Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids
Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids
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DOI：
10.1172/jci119160
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发表时间：
1997-01-15
影响因子：
15.9
通讯作者：
Wright, SD
中科院分区：
文献类型：
--
作者：
Yu, B;Hailman, E;Wright, SD
脂多糖结合蛋白（LBP）是已知促进细菌LPS（内毒素）扩散的血浆蛋白。LBP催化LPS单体从LPS聚集体移动到HDL颗粒、磷脂双层和第二血浆蛋白可溶性CD 14（sCD 14）上的结合位点。sCD 14可以通过从LPS聚集体接收LPS单体，然后将其交给HDL颗粒来加速转移，从而充当不溶性脂质的可溶性“穿梭"。在这里，我们表明LBP和sCD 14不仅穿梭LPS，而且还穿梭磷脂。磷脂酰肌醇（PI）、磷脂酰胆碱和荧光标记的磷脂酰乙醇胺衍生物（R-PE）各自通过LBP从膜转移到HDL颗粒。用重组LBP和sCD 14或全人血浆均可观察到PI的转移，抗LBP可阻断PI的血浆介导的转移，抗CD 14可部分抑制PI的血浆介导的转移。sCD 14似乎充当磷脂的可溶性穿梭物，因为观察到PI和R-PE与sCD 14的直接结合，并且因为添加sCD 14加速了这些脂质的转移。这些研究定义了LBP和sCD 14的新功能，并描述了磷脂在血液中转移的新机制。在进一步的研究中，我们发现的证据表明，LBP转移LPS和磷脂的相互交换：LBP催化结合的R-PE的LPS。sCD 14复合物伴随着LPS从sCD 14中退出，并且LPS与sCD 14的预先结合加速了LBP催化的R-PE与sCD 14的结合。因此，一种脂质的结合与第二种脂质的释放在功能上耦合。这些结果表明，LBP作为一种脂质交换蛋白。
Lipopolysaccharide binding protein (LBP) is a plasma protein known to facilitate the diffusion of bacterial LPS (endotoxin). LBP catalyzes movement of LPS monomers from LPS aggregates to HDL particles, to phospholipid bilayers, and to a binding site on a second plasma protein, soluble CD14 (sCD14). sCD14 can hasten transfer by receiving an LPS monomer from an LPS aggregate, and then surrendering it to an HDL particle, thus acting as a soluble ''shuttle'' for an insoluble lipid. Here we show that LBP and sCD14 shuttle not only LPS, but also phospholipids. Phosphatidylinositol (PI), phosphatidylcholine, and a fluorescently labeled derivative of phosphatidylethanolamine (R-PE) are each transferred by LBP from membranes to HDL particles. The transfer could be observed using recombinant LBP and sCD14 or whole human plasma, and the plasma-mediated transfer of PI could be blocked by anti-LBP and partially inhibited by anti-CD14. sCD14 appears to act as a soluble shuttle for phospholipids since direct binding of PI and R-PE to sCD14 was observed and because addition of sCD14 accelerated transfer of these lipids. These studies define a new function for LBP and sCD14 and describe a novel mechanism for the transfer of phospholipids in blood. In further studies, we show evidence suggesting that LBP transfers LPS and phospholipids by reciprocal exchange: LBP-catalyzed binding of R-PE to LPS . sCD14 complexes was accompanied by the exit of LPS from sCD14, and LBP-catalyzed binding of R-PE to sCD14 was accelerated by prior binding of LPS to sCD14. Binding of one lipid is thus functionally coupled with the release of a second. These results suggest that LBP acts as a lipid exchange protein.