Integrin-associated protein immunoglobulin domain is necessary for efficient vitronectin bead binding
Integrin-associated protein immunoglobulin domain is necessary for efficient vitronectin bead binding
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DOI：
10.1083/jcb.134.5.1313
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发表时间：
1996-09-01
影响因子：
7.8
通讯作者：
Brown, EJ
中科院分区：
文献类型：
--
作者：
Lindberg, FP;Gresham, HD;Brown, EJ
整合素相关蛋白 (IAP/CD47) 与 α(v) beta(3) 玻连蛋白 (Vn) 受体以及中性粒细胞 (PMN) 和单核细胞上功能和免疫学相关的整合素物理相关。抗 IAP 抗体抑制多种吞噬细胞功能，包括 Arg-Gly-Asp (RGD) 启动的吞噬作用、趋化性和呼吸爆发的激活； PMN 与巢蛋白的粘附；以及中性粒细胞跨内皮和跨上皮迁移，紧随细胞间紧密粘附。抗 IAP 抗体还抑制 Vn 包被颗粒与许多表达 alpha(v) beta(3) 的细胞的结合。然而，先前的抗 IAP 研究并没有直接解决 IAP 功能，因为它们无法区分 IAP 阻断和抗体诱导的细胞信号传导效应。为了更好地确定 IAP 的功能，我们表征并使用了 IAP 缺陷的人类细胞系。尽管表达 α(v) 整联蛋白，但这些细胞不会结合 Vn 包被的颗粒，除非用 IAP 表达构建体转染。增加颗粒上的 alpha(v) beta(3) 表达水平或增加 Vn 密度并不能克服 IAP 的要求。所有已知的 IAP 剪接变体均等价地恢复 Vn 颗粒结合。事实上，膜锚定的 IAP Ig 可变结构域足以介导该系统中的 Vn 颗粒结合，而多重跨膜和细胞质结构域是可有可无的。在所有情况下，对 Vn 包被表面的粘附以及通过 α(5) β(1) 纤连蛋白受体结合的纤连蛋白颗粒与 IAP 表达无关。这些数据表明，一些或整联蛋白配体结合功能是独立于IAP的，而另一些则需要IAP，大概是通过其Ig结构域和整联蛋白之间的直接物理相互作用。
Integrin-associated protein (IAP/CD47) is physically associated with the alpha(v) beta(3) vitronectin (Vn) receptor and a functionally and immunologically related integrin on neutrophils (PMN) and monocytes. Anti-IAP antibodies inhibit multiple phagocyte functions, including Arg-Gly-Asp (RGD)-initiated activation of phagocytosis, chemotaxis, and respiratory burst; PMN adhesion to entactin; and PMN transendothelial and transepithelial migration at a step subsequent to tight intercellular adhesion. Anti-IAP antibodies also inhibit binding of Vn-coated particles to many cells expressing alpha(v) beta(3). However, prior studies with anti-IAP did not directly address IAP function because they could not distinguish between IAP blockade and antibody-induced signaling effects on cells, To better determine the function of IAP, we have characterized and used an IAP-deficient human cell line, Despite expressing alpha(v) integrins, these cells do not bind Vn-coated particles unless transfected with IAP expression constructs. Increasing the level of alpha(v) beta(3) expression or increasing Vn density on the particle does not overcome the requirement for IAP. All known splice variants of IAP restore Vn particle binding equivalently, Indeed, the membrane-anchored IAP Ig variable domain suffices to mediate Vn particle binding in this system, while the multiply membrane-spanning and cytoplasmic domains are dispensable. In all cases, adhesion to a Vn-coated surface and fibronectin particle binding through alpha(5) beta(1) fibronectin receptors are independent of IAP expression. These data demonstrate that some or, integrin ligand-binding functions are IAP independent, whereas others require IAP, presumably through direct physical interaction between its Ig domain and the integrin.