Macrophage surface expression of annexins I and II in the phagocytosis of apoptotic lymphocytes
Macrophage surface expression of annexins I and II in the phagocytosis of apoptotic lymphocytes
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DOI：
10.1091/mbc.e03-09-0670
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发表时间：
2004-06-01
影响因子：
3.3
通讯作者：
Schlegel, RA
中科院分区：
文献类型：
--
作者：
Fan, XX;Krahling, S;Schlegel, RA
当细胞经历凋亡或程序性细胞死亡时，它们在其表面上暴露磷脂酰丝氨酸（PS）。有效吞噬凋亡细胞的巨噬细胞也在其表面表达PS，尽管水平较低。暴露在两个细胞上的PS是吞噬作用所必需的，因为通过用膜联蛋白V（一种PS结合蛋白）掩蔽任一细胞上的PS来抑制摄取。这种抑制不是加和的，表明两种细胞上暴露的PS分子参与了一个共同的过程。我们询问这种双重要求是否反映了靶细胞和巨噬细胞通过二价PS结合膜联蛋白的桥接。抗膜联蛋白I或II的单克隆抗体（mAb）染色的各种活吞噬细胞。凋亡的Jurkat T淋巴细胞和人外周血T淋巴细胞，但不是凋亡的胸腺细胞，被染色的抗膜联蛋白I，但不II。通过膜联蛋白I或II的单克隆抗体或通过用相同的单克隆抗体预处理巨噬细胞来抑制凋亡靶的吞噬作用。预处理凋亡的胸腺细胞没有影响，而预处理Jurkat细胞与抗膜联蛋白I或去除膜联蛋白I与EGTA的抑制。膜联蛋白桥接是矢量的，因为膜联蛋白结合到目标上的PS分子，而不是在巨噬细胞上，这表明膜联蛋白在促进吞噬作用中充当配体和受体。
When cells undergo apoptosis, or programmed cell death, they expose phosphatidylserine (PS) on their surface. Macrophages that efficiently phagocytose apoptotic cells also express PS on their surface, although at a lower level. The PS exposed on both cells is required for phagocytosis, because uptake is inhibited by masking PS on either cell with annexin V, a PS-binding protein. The inhibition is not additive, suggesting that the exposed PS molecules on the two cells participate in a common process. We asked whether this dual requirement reflects bridging of the target cell and macrophage by bivalent, PS-binding annexins. Monoclonal antibodies (mAbs) against annexins I or II stained a variety of live phagocytes. Apoptotic Jurkat T lymphocytes and human peripheral T lymphocytes, but not apoptotic thymocytes, were stained by anti-annexin I but not II. Phagocytosis of apoptotic targets was inhibited by mAbs to annexins I or II, or by pretreatment of macrophages with the same mAbs. Pretreatment of apoptotic thymocytes had no effect, whereas pretreating Jurkat cells with anti-annexin I or removing annexin I with EGTA was inhibitory. Annexin bridging is vectorial, because annexin is bound to PS molecules on targets but not on macrophages, suggesting annexins serve as both ligand and receptor in promoting phagocytosis.