macrophages: Role of membrane phosphatidylserine

macrophages: Role of membrane phosphatidylserine
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DOI:
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发表时间:
2005
影响因子:
11.1
通讯作者:
Gilberto R. Sambrano;D. Steinberg
Gilberto R. Sambrano;D. Steinberg
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gilberto R. Sambrano;D. Steinberg

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我们最近报道,氧化低密度脂蛋白 (OxLDL),而非乙酰 LDL (AcLDL),抑制小鼠腹膜巨噬细胞对非调理作用的氧化损伤红细胞 (OxRBC) 的结合和吞噬作用,这意味着除 AcLDL 受体外还有“清道夫受体”参与其中。大量研究表明,质膜磷脂不对称性的丧失会增加膜外层磷脂酰丝氨酸的表达,在巨噬细胞识别受损细胞和凋亡细胞中发挥关键作用。我们在此报告,这种识别部分归因于识别 OxLDL 的相同小鼠巨噬细胞受体。正如随附论文中所述,这是一种 94-97 kDa 的质膜蛋白。磷脂酰丝氨酸脂质体显示出与相同的 94 至 97-kDa 蛋白质的强配体结合,并且这种结合被 OxLDL 抑制,但不被 AcLDL 抑制。通过与钒酸钠一起孵育来抑制红细胞膜磷脂转位酶,导致细胞表面磷脂酰丝氨酸的出现逐渐增加,并且这些红细胞与巨噬细胞的结合也平行增加,这种结合被OxLDL抑制。最后,OxLDL 还抑制镰状红细胞和凋亡胸腺细胞与小鼠巨噬细胞的结合。然而,后者是不完整的('509o),表明其他受体也参与其中。我们认为 OxLDL 受体在识别受损和凋亡细胞中发挥着重要作用。
We recently reported that oxidized low density lipoprotein (OxLDL), but not acetyl LDL (AcLDL), inhibited the binding and phagocytosis of nonopsonized, oxidatively damaged red blood cells (OxRBCs) by mouse peritoneal macrophages, implying the involvement of a "scavenger receptor" other than the AcLDL receptor. Numerous studies establish that loss of plasma membrane phospholipid asymmetry, which increases phosphatidylserine expression on the outer leaflet of the membrane, can play a key role in macrophage recognition of damaged and apoptotic cells. We report here that this recognition is in part attributable to the same mouse macrophage receptor that recognizes OxLDL. As described in an accompanying paper, this is a plasma membrane protein of 94-97 kDa. Phosphatidylserine liposomes show strong ligand binding to the same 94to 97-kDa protein and this binding is inhibited by OxLDL but not by AcLDL. Inhibition of the RBC membrane phospholipid translocase by incubation with sodium vanadate caused a progressive increase in the appearance of phosphatidylserine on the cell surface and a parallel increase in the binding of these RBCs to macrophages, binding that was inhibited by OxLDL. Finally, OxLDL also inhibited the binding of sickled RBCs and apoptotic thymocytes to mouse macrophages. However, the latter was incomplete ('509o), suggesting that other receptors are also involved. We suggest that the OxLDL receptor plays a significant role in recognition of damaged and apoptotic