Dimeric galectin-1 induces surface exposure of phosphatidylserine and phagocytic recognition of leukocytes without inducing apoptosis
Dimeric galectin-1 induces surface exposure of phosphatidylserine and phagocytic recognition of leukocytes without inducing apoptosis
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DOI：
10.1074/jbc.m306624200
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发表时间：
2003-10-17
影响因子：
4.8
通讯作者：
Cummings, RD
中科院分区：
文献类型：
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作者：
Dias-Baruffi, M;Zhu, H;Cummings, RD
我们报告，人半乳糖凝集素-1（dGal-1），一种小的二聚体β-半乳糖苷结合蛋白，诱导磷脂酰丝氨酸（PS）暴露，通过膜联蛋白V染色测量，对人早幼粒细胞HL-60细胞，T白血病MOLT-4细胞，和fMet-Leu-Phe激活，但不休息，人中性粒细胞。dGal-1对HL-60和MOLT-4细胞的这种作用通过用神经氨酸酶预处理细胞而增强，但用神经氨酸酶处理静息中性粒细胞并不增强其对dGal-1的敏感性。虽然用膜联蛋白V染色的诱导通常与细胞凋亡相关，但dGal-1处理的HL-60细胞、MOLT-4细胞和活化的中性粒细胞不经历细胞凋亡，并且没有可检测的DNA片段化。用dGal-1处理的HL-60和MOLT-4细胞继续正常生长。相比之下，喜树碱处理的HL-60细胞，依托泊苷处理的MOLT-4细胞，和抗Fas处理的中性粒细胞表现出广泛的DNA断裂和/或细胞死亡。乳糖抑制dGal-1诱导的作用，表明dGal-1诱导的信号传导需要与细胞表面β-半乳糖苷结合。Gal-1的二聚体形式是信号传导所必需的，因为Gal-1的单体突变形式，称为mGal-1，与细胞结合但不引起这些作用。重要的是，HL-60细胞和活化的人嗜中性粒细胞的dGal-1而不是mGal-1处理显著促进它们被活化的小鼠巨噬细胞吞噬。这些dGal-1诱导的作用与凋亡不同，但与凋亡剂一样，使细胞准备用于吞噬去除。dGal-1的这种作用可能有助于白细胞稳态。
We report that human galectin-1 (dGal-1), a small dimeric beta-galactoside-binding protein, induces phosphatidylserine ( PS) exposure, measured by Annexin V staining, on human promyelocytic HL-60 cells, T leukemic MOLT-4 cells, and fMet-Leu-Phe-activated, but not resting, human neutrophils. This effect of dGal-1 on HL-60 and MOLT-4 cells is enhanced by pretreatment of the cells with neuraminidase, but treatment of resting neutrophils with neuraminidase does not enhance their sensitivity to dGal-1. Although the induction of staining with Annexin V is often associated with apoptosis, the dGal-1-treated HL-60 cells, MOLT-4 cells, and activated neutrophils do not undergo apoptosis, and there is no detectable DNA fragmentation. HL-60 and MOLT-4 cells treated with dGal-1 continue to grow normally. By contrast, camptothecin-treated HL-60 cells, etoposide-treated MOLT-4 cells, and anti-Fas-treated neutrophils exhibit extensive DNA fragmentation and/or cell death. Lactose inhibits the dGal-1-induced effects, indicating that dGal-1-induced signaling requires binding to cell surface beta-galactosides. The dimeric form of Gal-1 is required for signaling, because a monomeric mutant form of Gal-1, termed mGal-1, binds to cells but does not cause these effects. Importantly, dGal-1, but not mGal-1, treatment of HL-60 cells and activated human neutrophils significantly promotes their phagocytosis by activated mouse macrophages. These dGal-1-induced effects are distinguishable from apoptosis, but like apoptotic agents, prepare cells for phagocytic removal. Such effects of dGal-1 may contribute to leukocyte homeostasis.