Plasma constituents regulate LPS binding to, and release from, the monocyte cell surface
Plasma constituents regulate LPS binding to, and release from, the monocyte cell surface
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DOI：
10.1179/096805100101532450
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发表时间：
2000-01-01
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影响因子：
--
通讯作者：
Munford, RS
中科院分区：
文献类型：
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作者：
Kitchens, RL;Thompson, PA;Munford, RS
对革兰氏阴性菌的先天免疫涉及调节机制，允许对LPS敏感但有限的反应。导致宿主细胞活化和脂多糖失活的两个重要途径包括：(i)脂多糖与细胞上的CD14和toil样受体4的相互作用（激活）和（ii）脂多糖被血浆脂蛋白隔离（失活）。虽然这些途径以前被认为是独立的，基本上是不可逆的，但我们发现它们通过第三种途径连接起来：（iii） LPS从宿主细胞到血浆脂蛋白的运动。我们的数据表明，在人血浆存在的情况下，LPS与单核细胞表面短暂结合，然后从细胞表面转移到血浆脂蛋白。可溶性CD14促进脂多糖在脂蛋白存在下从细胞释放，而脂多糖结合蛋白和磷脂转移蛋白则没有。细胞结合脂多糖向脂蛋白的转移伴随着细胞对脂多糖反应的降低。这表明LPS从白细胞转移到脂蛋白可能会减弱宿主体内对LPS的反应。初步数据表明，创伤后或败血症期间血浆中发生的变化减少了LPS与白细胞的结合，同时大大增加了LPS从细胞中释放的速度。
Innate immunity to Gram-negative bacteria involves regulated mechanisms that allow sensitive but limited responses to LPS. Two important pathways that lead to host cell activation and LPS deactivation involve: (i) LPS interactions with CD14 and Toil-like receptor 4 on cells (activation), and (ii) LPS sequestration by plasma lipoproteins (deactivation). Whereas these pathways were previously thought to be independent and essentially irreversible, we found that they are connected by a third pathway: (iii) the movement of LPS from host cells to plasma lipoproteins. Our data show that, in the presence of human plasma, LPS binds transiently to monocyte surfaces and then moves from the cell surface to plasma lipoproteins. Soluble CD14 enhances LPS release from cells in the presence of lipoproteins, whereas LPS binding protein and phospholipid transfer protein do not, The transfer of cell-bound LPS to lipoproteins is accompanied by reduced cell responses to the LPS. suggesting that the movement of LPS from leukocytes into lipoproteins may attenuate host responses to LPS in vivo. Preliminary data suggest that changes that occur in the plasma after trauma or during sepsis decrease LPS binding to leukocytes while greatly increasing the rate of LPS release from cells.