Soluble CD14 acts as a shuttle in the neutralization of lipopolysaccharide (LPS) by LPS-binding protein and reconstituted high density lipoprotein.

Soluble CD14 acts as a shuttle in the neutralization of lipopolysaccharide (LPS) by LPS-binding protein and reconstituted high density lipoprotein.
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可溶性CD14充当LPS结合蛋白和重构的高密度脂蛋白的脂多糖(LPS)中和的班车。

DOI:
10.1084/jem.181.5.1743
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发表时间:
1995-05-01
影响因子:
15.3
通讯作者:
Wright, Samuel D.
Wright, Samuel D.
中科院分区:
医学1区
文献类型:
--
作者:
Wurfel, Mark M.;Hailman, Eric;Wright, Samuel D.

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我们最近发现,脂多糖(LPS)结合蛋白(LBP)是一种脂质转移蛋白,催化两个不同的反应:移动的细菌LPS(内毒素)从LPS胶束可溶性CD 14(sCD 14)和移动的LPS从胶束重组高密度脂蛋白(R-HDL)颗粒。在这里,我们表明,LBP促进第三脂质转移反应:LPS从LPS-sCD 14复合物移动到R-HDL颗粒。LBP的这种作用是催化性的,一个LBP分子使多个LPS分子能够移动到R-HDL中。LBP催化的LPS从LPS-sCD 14复合物向R-HDL的移动中和了LPS刺激多形核白细胞的能力。我们的研究结果表明,LPS可以通过LBP的直接作用或通过两步反应转移到R-HDL,其中LPS首先转移到sCD 14,随后转移到R-HDL。我们已经观察到LPS转移到R-HDL的两步途径比直接转移更有利。加入sCD 14可使LBP和R-HDL对LPS的中和作用加速30倍以上。几个观察结果表明sCD 14通过充当LPS的穿梭体而加速该反应:将LBP和sCD 14加入LPS胶束中导致LPS-sCD 14复合物可以扩散通过100-kD的截止过滤器,LPS-sCD 14复合物在LPS向R-HDL移动期间短暂出现,而纯化的LBP促进了LPS向R-HDL的移动。sCD 14可促进LPS向R-HDL的转移而不成为最终LPS-R-HDL复合物的一部分。LPS与sCD 14的复合物在血浆中孵育时瞬时形成,表明这些复合物在生理条件下可能作为中和LPS的中间体发挥作用。这些发现详细说明了sCD 14的新活性,并提出了LBP脂质转移的新机制。
We have recently shown that lipopolysaccharide (LPS)-binding protein (LBP) is a lipid transfer protein that catalyzes two distinct reactions: movement of bacterial LPS (endotoxin) from LPS micelles to soluble CD14 (sCD14) and movement of LPS from micelles to reconstituted high density lipoprotein (R-HDL) particles. Here we show that LBP facilitates a third lipid transfer reaction: movement of LPS from LPS- sCD14 complexes to R-HDL particles. This action of LBP is catalytic, with one molecule of LBP enabling the movement of multiple LPS molecules into R-HDL. LBP-catalyzed movement of LPS from LPS-sCD14 complexes to R-HDL neutralizes the capacity of LPS to stimulate polymorphonuclear leukocytes. Our findings show that LPS may be transferred to R-HDL either by the direct action of LBP or by a two- step reaction in which LPS is first transferred to sCD14 and subsequently to R-HDL. We have observed that the two-step pathway of LPS transfer to R-HDL is strongly favored over direct transfer. Neutralization of LPS by LBP and R-HDL was accelerated more than 30- fold by addition of sCD14. Several observations suggest that sCD14 accelerates this reaction by serving as a shuttle for LPS: addition of LBP and sCD14 to LPS micelles resulted in LPS-sCD14 complexes that could diffuse through a 100-kD cutoff filter; LPS-sCD14 complexes appeared transiently during movement of LPS to R-HDL facilitated by purified LBP; and sCD14 could facilitate transfer of LPS to R-HDL without becoming part of the final LPS-R-HDL complex. Complexes of LPS and sCD14 were formed transiently when LPS was incubated in plasma, suggesting that these complexes may play a role as intermediates in the neutralization of LPS under physiological conditions. These findings detail a new activity for sCD14 and suggest a novel mechanism for lipid transfer by LBP.
DOI: 10.1126/science.1698311
发表时间: 1990-09-21
期刊: SCIENCE
影响因子: 56.9
作者:
WRIGHT, SD;RAMOS, RA;MATHISON, JC
通讯作者: MATHISON, JC
DOI: 10.1089/hyb.1.1982.1.329
发表时间: 1982-01-01
期刊: HYBRIDOMA
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通讯作者: TERHORST, C
DOI: 10.1128/iai.61.12.5140-5146.1993
发表时间: 1993-12-01
影响因子: 3.1
作者:
FLEGEL, WA;BAUMSTARK, MW;NORTHOFF, H
通讯作者: NORTHOFF, H
DOI: 10.1073/pnas.80.18.5699
发表时间: 1983-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
WRIGHT, SD;RAO, PE;SILVERSTEIN, SC
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DOI: 10.1084/jem.179.1.269
发表时间: 1994-01-01
期刊: The Journal of experimental medicine
影响因子: --
作者:
Hailman E;Lichenstein HS;Wurfel MM;Miller DS;Johnson DA;Kelley M;Busse LA;Zukowski MM;Wright SD
通讯作者: Wright SD