ANTI-BETA-1 INTEGRIN ANTIBODY INHIBITS SCHWANN-CELL MYELINATION

Schwann cells (SCs) co-cultured with sensory neurons require ascorbate supplementation for basal lamina assembly and differentiation into my elinating cells. The ascorbate requirement can be bypassed by adding a purified basal lamina component, laminin, to SC/neuron cocultures. We have examined the role of laminin receptors, namely, the pi subfamily of integrins, in the process of myelination. We demonstrate by immuno staining or immunoprecipitation that undifferentiated SCs in contact w ith axons express large amounts of the pi subunit in association with the alpha 1 or alpha 6 subunit. In co-cultures of myelinating SCs, alp ha 1 beta 1 is no longer present, alpha 6 beta 1 is still present but at reduced levels, and alpha 6 alpha 1 is expressed at much higher lev els than in co-cultures of undifferentiated SCs. Immunogold labelling at the electron microscope level suggested that beta 1 integrins are r andomly distributed on undifferentiated SCs, become localized to the S C surface contacting basal lamina in differentiating SCs before the on set of myelination, and are not detected on myelinating SCs. Fab fragm ents of beta 1 function-blocking antibody block both attachment of iso lated SCs to laminin and formation of myelin sheaths by SCs co-culture d with neurons in ascorbate-supplemented medium. SCs unable to myelina te in the presence of the anti-beta 1 antibody assemble patchy basal l amina that is only loosely attached to the cell surface and in some ca ses appears to be detaching from the membrane. In contrast, an alpha 1 p beta 1 function-blocking antibody only partially blocks attachment o f isolated SCs to laminin but has no inhibitory effect on SC myelinati on. These results are consistent with the hypothesis that a member of the beta 1 subfamily of integrins other than alpha 1 beta 1 binds lami nin present in basal lamina to the SC surface and transduces signals t hat are critical for initiation of SC differentiation into a myelinati ng cell. (C) 1994 John Wiley and Sons, Inc.