Yu B, Hailman E, Wright S D
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021, USA.
J Clin Invest. 1997 Jan 15;99(2):315-24. doi: 10.1172/JCI119160.
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 x 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.
脂多糖结合蛋白（LBP）是一种血浆蛋白，已知其可促进细菌脂多糖（内毒素）的扩散。LBP催化脂多糖单体从脂多糖聚集体向高密度脂蛋白颗粒、磷脂双层以及第二种血浆蛋白可溶性CD14（sCD14）上的结合位点移动。sCD14可以通过从脂多糖聚集体接收一个脂多糖单体，然后将其交给高密度脂蛋白颗粒来加速转移，从而作为一种不溶性脂质的可溶性“穿梭载体”。在这里我们表明，LBP和sCD14不仅穿梭运输脂多糖，还穿梭运输磷脂。磷脂酰肌醇（PI）、磷脂酰胆碱以及磷脂酰乙醇胺的荧光标记衍生物（R-PE）均可被LBP从膜转移至高密度脂蛋白颗粒。使用重组LBP和sCD14或全人血浆均可观察到这种转移，并且PI的血浆介导转移可被抗LBP抗体阻断，并被抗CD14抗体部分抑制。sCD14似乎作为磷脂的可溶性穿梭载体，因为观察到PI和R-PE与sCD14直接结合，并且添加sCD14可加速这些脂质的转移。这些研究确定了LBP和sCD14的新功能，并描述了血液中磷脂转移的新机制。在进一步的研究中，我们显示有证据表明LBP通过相互交换来转移脂多糖和磷脂：LBP催化R-PE与脂多糖×sCD14复合物的结合伴随着脂多糖从sCD14上的释放，并且LPS预先与sCD14结合可加速LBP催化的R-PE与sCD14的结合。因此，一种脂质的结合在功能上与另一种脂质的释放相关联。这些结果表明LBP作为一种脂质交换蛋白发挥作用。
