Wu C, Fields A J, Kapteijn B A, McDonald J A
Samule C. Johnson Medical Research Center, Mayo Clinic Scottsdale, AZ 85259, USA.
J Cell Sci. 1995 Feb;108 ( Pt 2):821-9. doi: 10.1242/jcs.108.2.821.
The alpha 4 beta 1 integrin has been suggested to play important roles in embryogenesis and pathogenesis of many diseases which involve both cell adhesion and cell migration. Previous studies using anti-alpha 4 beta 1 antibodies and fibronectin (Fn) fragments have suggested that alpha 4 beta 1 integrins may be involved in cell motility on Fn and vascular cell adhesion molecule-1 (VCAM-1). However, the cells used in these studies also express other Fn integrin receptors including alpha 5 beta 1 integrin, which is known to function in cell motility on Fn. To test whether alpha 4 beta 1 integrins mediate cell motility on Fn and VCAM-1 in the absence of alpha 5 beta 1 integrin, we expressed human alpha 4 integrin in a Chinese hamster ovary (CHO) cell line that is deficient in alpha 5 beta 1 integrin (CHO B2). The parental alpha 5 deficient CHO B2 cells were unable to adhere, spread or migrate on Fn, nor could they assemble a fibrillar Fn matrix. Expression of alpha 4 beta 1 integrin in the CHO B2 cells enabled the cells to adhere, spread and migrate on Fn and on VCAM-1 but not to assemble a fibrillar Fn matrix. The cellular processes mediated by the interaction of alpha 4 beta 1 with Fn or VCAM-1 were inhibited by the CS1 peptide derived from the major alpha 4 beta 1 binding site on Fn. These findings demonstrate that alpha 4 beta 1 integrins not only function as cell adhesion receptors but also as cell motility receptors for Fn and VCAM-1 independent of alpha 5 beta 1. Moreover, they reveal important functional differences between Fn binding integrins. The alpha 4-positive, alpha 5-negative CHO cells described in this report will be useful tools in studying the mechanism of molecular signalling during integrin mediated cellular processes.
α4β1整合素被认为在胚胎发育以及许多涉及细胞黏附和细胞迁移的疾病发病机制中发挥重要作用。以往使用抗α4β1抗体和纤连蛋白（Fn）片段的研究表明，α4β1整合素可能参与细胞在Fn和血管细胞黏附分子-1（VCAM-1）上的运动。然而，这些研究中使用的细胞也表达其他Fn整合素受体，包括α5β1整合素，已知其在细胞在Fn上的运动中发挥作用。为了测试在不存在α5β1整合素的情况下，α4β1整合素是否介导细胞在Fn和VCAM-1上的运动，我们在中国仓鼠卵巢（CHO）细胞系中表达人α4整合素，该细胞系缺乏α5β1整合素（CHO B2）。亲本α5缺陷型CHO B2细胞无法在Fn上黏附、铺展或迁移，也不能组装纤维状Fn基质。在CHO B2细胞中表达α4β1整合素使细胞能够在Fn和VCAM-1上黏附、铺展和迁移，但不能组装纤维状Fn基质。由α4β1与Fn或VCAM-1相互作用介导的细胞过程被源自Fn上主要α4β1结合位点的CS1肽所抑制。这些发现表明，α4β1整合素不仅作为细胞黏附受体发挥作用，而且作为Fn和VCAM-1的细胞运动受体发挥作用，独立于α5β1。此外，它们揭示了Fn结合整合素之间重要的功能差异。本报告中描述的α4阳性、α5阴性CHO细胞将成为研究整合素介导的细胞过程中分子信号传导机制的有用工具。
