CD157 is an important mediator of neutrophil adhesion and migration
CD157 is an important mediator of neutrophil adhesion and migration
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DOI：
10.1182/blood-2004-06-2129
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发表时间：
2004-12-15
期刊：
影响因子：
20.3
通讯作者：
Malavasi, F
中科院分区：
文献类型：
--
作者：
Funaro, A;Ortolan, E;Malavasi, F
CD157是一种糖基磷脂酰肌醇（GPI）锚定蛋白，由CD38 NADase/ adp -核糖体环化酶基因家族成员编码，在大多数人类循环中性粒细胞表面表达。这项工作表明，CD157是一种诱导细胞骨架重组和细胞形状显著变化的受体，并且CD157介导的信号通过调节胞质Ca2+浓度起作用。这些信号独立于CD157酶活性的产物（即环腺苷二磷酸[ADP]-核糖和ADP-核糖）。事实上，CD157在循环中性粒细胞和二甲基亚砜（DMSO）分化(CD157(+)/CD38(-)) HL-60细胞中的酶活性几乎无法检测到。这项工作还表明，受体活性依赖于CD157和β(2)整合素之间的串扰。CD157定位于富含gm1的脂筏，激活后，它迁移到尾足，这是一种专门从事运动和粘附功能的结构。事实上，CD157参与了细胞外基质蛋白的粘附和甲氧基-蛋氨酸-亮氨酸-苯丙氨酸（fMLP）体外诱导的趋化作用。这些发现与在阵发性夜间血红蛋白尿（PNH）患者中性粒细胞中获得的结果一致，PNH患者CD157缺乏。这些中性粒细胞在粘附和迁移方面表现出持续的缺陷。我们的数据归因于CD157在炎症期间调节先天免疫中的特定和关键作用。(C) 2004年由美国血液病学会出版。
CD157, a glycosylphosphatidylinositol (GPI)-anchored protein encoded by a member of the CD38 NADase/ADP-ribosyl cyclase gene family, is expressed on the surface of most human circulating neutrophils. This work demonstrates that CD157 is a receptor that induces reorganization of the cytoskeleton and significant changes in cell shape, and that signals mediated by CD157 act through modulation of cytosolic Ca2+ concentration. These signals are independent of the products of CD157's enzymatic activities (ie, cyclic adenosine diphosphate [ADP]-ribose and ADP-ribose). Indeed, the enzymatic activities of CD157 in circulating neutrophils as well as in dimethyl sulfoxide (DMSO)-differentiated (CD157(+)/CD38(-)) HL-60 cells, are hardly detectable. This work also shows that the receptorial activity relies on cross-talk between CD157 and beta(2) integrin. CD157 localizes in GM1-enriched lipid rafts and, upon activation, it migrates to the uropod, a structure specialized in motility and adhesive functions. Indeed, CD157 is involved in adhesion to extracellular matrix proteins and in chemotaxis induced in vitro by formyl-methionyl-leucyl-phenylalanine (fMLP). These findings were consistent with the results obtained in neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH), in which CD157 is deficient. These neutrophils showed constant defects in adhesion and migration. Our data attribute specific and crucial roles to CD157 in the regulation of innate immunity during inflammation. (C) 2004 by The American Society of Hematology.