Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells
Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells
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DOI：
10.1172/jci34487
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发表时间：
2008-05-01
影响因子：
15.9
通讯作者：
Bonventre, Joseph V.
中科院分区：
文献类型：
--
作者：
Ichimura, Takaharu;Asseldonk, Edwin J. P. v.;Bonventre, Joseph V.
损伤后，凋亡和坏死细胞的清除对于减轻和解决炎症和组织修复是必要的。除了巨噬细胞，这是传统上分配给这个任务，在受影响的组织中的相邻上皮细胞被假定为有助于这一过程。肾损伤分子-1（KIM-1或TIM-1）是一种免疫球蛋白超家族细胞表面蛋白，不被髓系细胞表达，但在受损的肾上皮细胞表面高度上调。在这里，我们证明，受伤的肾上皮细胞假定内源性吞噬细胞的属性。共聚焦图像证实了在体内大鼠肾小管损伤后表达KIM-1的上皮细胞内凋亡小体的内化。KIM-1直接负责培养的原代大鼠肾小管上皮细胞以及猪和犬上皮细胞系中的吞噬作用。KIM-1能够特异性识别凋亡细胞表面特异性表位磷脂酰丝氨酸和氧化脂蛋白，表达凋亡肾小管上皮细胞。因此，KIM-1是第一个非髓磷脂酰丝氨酸受体确定我们的知识，将上皮细胞转化为半专业吞噬细胞。
Following injury, the clearance of apoptotic and necrotic cells is necessary for mitigation and resolution of inflammation and tissue repair. In addition to macrophages, which are traditionally assigned to this task, neighboring epithelial cells in the affected tissue are postulated to contribute to this process. Kidney injury molecule-1 (KIM-1 or TIM-1) is an immunoglobulin superfamily cell-surface protein not expressed by cells of the myeloid lineage but highly upregulated on the surface of injured kidney epithelial cells. Here we demonstrate that injured kidney epithelial cells assumed attributes of endogenous phagocytes. Confocal images confirm internalization of apoptotic bodies within KIM-1-expressing epithelial cells after injury in rat kidney tubules in vivo. KIM-1 was directly responsible for phagocytosis in cultured primary rat tubule epithelial cells and also porcine and canine epithelial cell lines. KIM-1 was able to specifically recognize apoptotic cell surface-specific epitopes phosphatidylserine, and oxidized lipoproteins, expressed by apoptotic tubular epithelial cells. Thus, KIM-1 is the first nonmyeloid phosphatidylserine receptor identified to our knowledge that transforms epithelial cells into semiprofessional phagocytes.