Milner R, Wilby M, Nishimura S, Boylen K, Edwards G, Fawcett J, Streuli C, Pytela R, ffrench-Constant C
Wellcome/CRC Institute of Developmental Biology and Cancer, Cambridge, United Kingdom.
Dev Biol. 1997 May 15;185(2):215-28. doi: 10.1006/dbio.1997.8547.
Myelination of the peripheral nervous system (PNS) requires the migration of Schwann cells during both development and regeneration. We have characterized the expression pattern of Schwann cell integrins and analyzed their role in migration on different ECM substrates known to be present within the PNS. We found that Schwann cells in cell culture express four beta1 integrins, alpha1 beta1, alpha2 beta1, alpha6 beta1, and another unidentified beta1 integrin, as well as two alpha v integrins, alpha v beta3 and alpha v beta8. Using the Varani migration assay, we found that laminin-1, laminin-2 (merosin), and fibronectin increased Schwann cell migration, while vitronectin and collagen did not increase migration compared to an uncoated plastic substrate. Schwann cell migration on laminin-1 and laminin-2 (merosin) was blocked by antibodies against beta1 integrins, but not affected by RGD peptides or antibodies against beta3 integrins. In contrast, migration on fibronectin was unaffected by antibodies against beta1 and beta3 integrins but was blocked by RGD peptides. This in vitro study shows that there is a division of labor of Schwann cell integrins in the regulation of migration on peripheral nerve ECM components; beta1 integrins mediate migration on laminin-1 and laminin-2 (merosin), while alpha v integrins mediate migration on fibronectin. Taken together, these results suggest that multiple interactions between Schwann cell integrins and ECM within the PNS will contribute to Schwann cell migration during myelination of the PNS.
外周神经系统（PNS）的髓鞘形成在发育和再生过程中都需要施万细胞的迁移。我们已经对施万细胞整合素的表达模式进行了表征，并分析了它们在已知存在于PNS中的不同细胞外基质（ECM）底物上迁移中的作用。我们发现，细胞培养中的施万细胞表达四种β1整合素，即α1β1、α2β1、α6β1和另一种未鉴定的β1整合素，以及两种αv整合素，αvβ3和αvβ8。使用瓦拉尼迁移试验，我们发现层粘连蛋白-1、层粘连蛋白-2（髓鞘素）和纤连蛋白可增加施万细胞迁移，而与未包被的塑料底物相比，玻连蛋白和胶原蛋白不会增加迁移。施万细胞在层粘连蛋白-1和层粘连蛋白-2（髓鞘素）上的迁移被抗β1整合素的抗体阻断，但不受RGD肽或抗β3整合素抗体的影响。相比之下，在纤连蛋白上的迁移不受抗β1和β3整合素抗体的影响，但被RGD肽阻断。这项体外研究表明，施万细胞整合素在调节外周神经ECM成分上的迁移中存在分工；β1整合素介导在层粘连蛋白-1和层粘连蛋白-2（髓鞘素）上的迁移，而αv整合素介导在纤连蛋白上的迁移。综上所述，这些结果表明，PNS内施万细胞整合素与ECM之间的多种相互作用将有助于PNS髓鞘形成过程中施万细胞的迁移。
