Convergence of the adhesive and fibrinolytic systems:: recognition of urokinase by integrin αMβ2 as well as by the urokinase receptor regulates cell adhesion and migration
Convergence of the adhesive and fibrinolytic systems:: recognition of urokinase by integrin αMβ2 as well as by the urokinase receptor regulates cell adhesion and migration
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DOI：
10.1182/blood-2002-06-1842
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发表时间：
2003-02-15
期刊：
影响因子：
20.3
通讯作者：
Plow, EF
中科院分区：
文献类型：
--
作者：
Pluskota, E;Soloviev, DA;Plow, EF
先前的研究表明，整合素α (M) β (2) （CD11b/18, Mac-1）在白细胞上与尿激酶型纤溶酶原激活物受体（uPAR/CD87）形成物理复合物。在这项研究中，我们使用人外周血中性粒细胞和表达α (M) β(2)、uPAR或两种受体的转染细胞来证明整合素可以直接与尿激酶（uPA）相互作用。我们证明α (M) β(2)支持这些细胞粘附和迁移到uPA，并且在每种情况下，阻断α (M) β(2)抑制了反应。在uPA中，kringle结构域和蛋白水解结构域都被α (M) β(2)识别，它们不同于与uPAR结合的生长因子结构域。在整合素的α (M)亚基中，I结构域与uPA相互作用，这与与uPAR相互作用的区域不同。在表达uPAR和α (M) β(2)的细胞上，这两种受体都介导了粘附和迁移。这种合作在中性粒细胞对uPA的反应中尤为明显，其中阻断α (M) β(2)减少了uPAR介导的反应，而uPAR的参与增强了α (M) β对uPA的识别(2)。因此，α (M) β(2)对uPA的识别允许形成多接触三分子复合物，其中单个uPA配体可以同时与uPAR和α (M) β(2)结合。该复合物可能在控制炎症细胞迁移和血管稳态中起重要作用。(C) 2003年由美国血液病学会出版。
Previous studies demonstrated that integrin alpha(M)beta(2) (CD11b/18, Mac-1) forms a physical complex with the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes. In this study, we used human peripheral blood neutrophils and transfected cells expressing alpha(M)beta(2), uPAR, or both receptors to show that the integrin can directly interact with urokinase (uPA). We demonstrate that alpha(M)beta(2) supported adhesion and migration of these cells to uPA, and, in each case, blockade Of alpha(M)beta(2) suppressed the response. Within uPA, both the kringle and proteolytic domains are recognized by alpha(M)beta(2), which are distinct from the growth factor domain that binds to uPAR. Within the alpha(M) subunit of the integrin, the I domain interacts with uPA, which is distinct from the region that interacts with uPAR. On cells expressing uPAR and alpha(M)beta(2), both receptors mediated adhesion and migration. This cooperation was particularly apparent in the responses of neutrophils to uPA, where blockade of alpha(M)beta(2) reduced uPAR-mediated responses and engagement of uPAR enhanced recognition of uPA by alpha(M)beta(2). Thus, recognition of uPA by alpha(M)beta(2) allows for formation of a multicontact trimolecular complex, in which a single uPA ligand may bind simultaneously to both uPAR and alpha(M)beta(2). This complex may play an important role in the control of inflammatory cell migration and vascular homeostasis. (C) 2003 by The American Society of Hematology.