Sonnenberg A, Linders C J, Modderman P W, Damsky C H, Aumailley M, Timpl R
Department of Immunohaematology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
J Cell Biol. 1990 Jun;110(6):2145-55. doi: 10.1083/jcb.110.6.2145.
The involvement of integrins in mediating interaction of cells to well-characterized proteolytic fragments (P1, E3, and E8) of laminin was assessed by antibody blocking studies. Cell adhesion to fragment P1 was affected by mAbs against the integrin beta 1 and beta 3 subunits and furthermore could be prevented completely by a synthetic peptide containing the Arg-Gly-Asp sequence. Because the beta 3 antibody-sensitive cell lines expressed the vitronectin receptor (alpha v beta 3) at high levels, the involvement of this receptor in cell adhesion to P1 is strongly suggested. Integrin-mediated cell adhesion to E3 is of low affinity and was inhibited by antibodies against the integrin beta 1 subunit. In contrast, adhesion of some cell types to E3 was not or only partially sensitive to inhibition by anti-integrin subunit antibodies. Cell adhesion to E8 was blocked completed by integrin alpha 6 or beta 1 antibodies. The alpha 6-specific antibody did not inhibit cell adhesion to E3 or P1. Furthermore, the antibody only blocked adhesion to laminin of those cells that adhered exclusively to the E8 fragment. In addition, expression of alpha 6 beta 1 was closely correlated with the ability of cells to bind to the E8 fragment of laminin. These results indicate that the alpha 6 beta 1 integrin is a specific receptor for the E8 fragment of laminin. Many cell types expressed, instead of or in addition to alpha 6 beta 1 the recently described integrin alpha 6 beta 4. Although the ligand of alpha 6 beta 4 was not identified, it must be different from that of alpha 6 beta 1, because cells that express alpha 6 beta 4, but not alpha 6 beta 1, do not adhere to E8, and cell adhesion to E8 was specifically blocked by beta 1 specific antibodies. In conclusion, the data indicate that distinct integrin receptors belonging to the beta 1 or beta 3 subfamily are involved in adhesion of cells to the various laminin fragments. Adhesion to E3 may also be brought about by other receptor molecules, possibly proteoglycans, not belonging to the integrin family.
通过抗体阻断研究评估整合素在介导细胞与层粘连蛋白特征明确的蛋白水解片段（P1、E3和E8）相互作用中的作用。针对整合素β1和β3亚基的单克隆抗体影响细胞对片段P1的黏附，此外，含有精氨酸-甘氨酸-天冬氨酸序列的合成肽可完全阻止这种黏附。由于β3抗体敏感的细胞系高水平表达玻连蛋白受体（αvβ3），强烈提示该受体参与细胞对P1的黏附。整合素介导的细胞对E3的黏附亲和力低，并被针对整合素β1亚基的抗体抑制。相反，某些细胞类型对E3的黏附对抗整合素亚基抗体的抑制不敏感或仅部分敏感。细胞对E8的黏附被整合素α6或β1抗体完全阻断。α6特异性抗体不抑制细胞对E3或P1的黏附。此外，该抗体仅阻断那些仅黏附于E8片段的细胞对层粘连蛋白的黏附。另外，α6β1的表达与细胞结合层粘连蛋白E8片段的能力密切相关。这些结果表明α6β1整合素是层粘连蛋白E8片段的特异性受体。许多细胞类型表达最近描述的整合素α6β4，以替代α6β1或与之同时表达。尽管未鉴定出α6β4的配体，但它肯定与α6β1不同，因为表达α6β4但不表达α6β1的细胞不黏附于E8，并且细胞对E8的黏附被β1特异性抗体特异性阻断。总之，数据表明属于β1或β3亚家族的不同整合素受体参与细胞对各种层粘连蛋白片段的黏附。对E3的黏附也可能由其他受体分子介导，可能是蛋白聚糖，它们不属于整合素家族。
