The role of integrin alpha D beta2 (CD11d/CD18) in monocyte/macrophage migration.
The role of integrin alpha D beta2 (CD11d/CD18) in monocyte/macrophage migration.
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DOI：
10.1016/j.yexcr.2008.05.016
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发表时间：
2008-08
影响因子：
3.7
通讯作者：
V. Yakubenko;N. Belevych;D. Mishchuk;A. Schurin;S. Lam;T. Ugarova
中科院分区：
文献类型：
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作者：
V. Yakubenko;N. Belevych;D. Mishchuk;A. Schurin;S. Lam;T. Ugarova
整合素αDβ2（CD 11 d/CD 18）是一种多配体巨噬细胞受体，其识别特异性与主要髓系细胞特异性整合素αMβ2（CD 11b/CD 18，Mac-1）相同。尽管αDβ 2对炎性巨噬细胞有显著的上调作用，但其在单核细胞和巨噬细胞迁移中的作用尚不清楚。在这项研究中，我们建立了表达不同密度αDβ 2的模型和天然细胞系，并检查了它们向各种细胞外基质蛋白的迁移。在低密度表达时，重组HEK 293细胞和小鼠IC-21巨噬细胞表面的αDβ 2与β1/β 3整合素协同支持细胞迁移。然而，其在表达αDβ2的HEK 293细胞上的表达增加和其在IC-21巨噬细胞上被PMA上调导致细胞增殖增加和细胞迁移抑制。此外，αDβ 2与抗α D阻断抗体的连接通过去除过量的αDβ2介导的粘附键来恢复β1/β3驱动的细胞迁移。与体外数据一致，给予抗α D抗体后，从小鼠炎症腹膜中回收的炎性巨噬细胞数量增加。这些结果表明，αDβ 2的密度在调节巨噬细胞粘附和迁移中起着关键作用，并提示低水平的αDβ 2有助于单核细胞迁移，而αDβ 2在分化的巨噬细胞上的上调可能有助于它们在炎症部位的滞留。
Integrin αDβ2(CD11d/CD18) is a multiligand macrophage receptor with recognition specificity identical to that of the major myeloid cell-specific integrin αMβ2(CD11b/CD18, Mac-1). Despite its prominent upregulation on inflammatory macrophages, the role of αDβ2in monocyte and macrophage migration is unknown. In this study, we have generated model and natural cell lines expressing different densities of αDβ2and examined their migration to various extracellular matrix proteins. When expressed at a low density, αDβ2on the surface of recombinant HEK293 cells and murine IC-21 macrophages cooperates with β1/β3integrins to support cell migration. However, its increased expression on the αDβ2-expressing HEK293 cells and its upregulation by PMA on the IC-21 macrophages result in increased cell adhesiveness and inhibition of cell migration. Furthermore, ligation of αDβ2with anti-αDblocking antibodies restores β1/β3-driven cell migration by removing the excess αDβ2-mediated adhesive bonds. Consistent with in vitro data, increased numbers of inflammatory macrophages were recovered from the inflamed peritoneum of mice after the administration of anti-αDantibody. These results demonstrate that the density of αDβ2is critically involved in modulating macrophage adhesiveness and their migration, and suggest that low levels of αDβ2contribute to monocyte migration while αDβ2upregulation on differentiated macrophages may facilitate their retention at sites of inflammation.