Astrocytes attenuate oligodendrocyte death in vitro through an α6 integrin-laminin-dependent mechanism

被引:62
作者
Corley, SM
Ladiwala, U
Besson, A
Yong, VW
机构
[1] Univ Calgary, Dept Oncol, Calgary, AB T2N 4N1, Canada
[2] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada
关键词
apoptosis; astrogliosis; extracellular matrix; myelination;
D O I
10.1002/glia.1116
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Oligodendrocyte (OL) death occurs in many disorders of the CNS, including multiple sclerosis and brain trauma. Factors reported to induce OL death include deprivation of growth factors, elevation of cytokines, oxidative stress, and glutamate excitotoxicity. Because astrocytes produce a large amount of growth factors and antioxidants and are a major source of glutamate uptake, we tested the hypothesis that astrocytes may have a protective role for OL survival. We report that when OLs from the adult mouse brain were initiated into tissue culture, DNA fragmentation and chromatin condensation resulted, indicative of apoptosis. OL death was significantly reduced in coculture with astrocytes, but not with fibroblasts, which provided a similar monolayer of cells as astrocytes. The protection of OL demise by astrocytes was not reproduced by its conditioned medium and was not accounted for by several neurotrophic factors. In contrast, interference with the a. integrin subunit, but not the alpha1, alpha2, alpha3, alpha4, alpha5, or alpha (v), integrin chains, negated astrocyte protection of OLs. Furthermore, a function-blocking antibody to alpha (6)beta (1) integrin reduced the ability of astrocytes to promote OL survival. The extracellular matrix ligand for alpha (6)beta (1) is laminin, which is expressed by astrocytes. Significantly, neutralizing antibodies to laminin-2 and laminin-5 inhibited the astrocyte mediation of OL survival. These results implicate astrocytes in promoting OL survival through a mechanism involving the interaction of alpha (6)beta (1) integrin on OLs with laminin on astrocytes. Enhancing this interaction may provide for OL survival in neurological injury. (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:281 / 294
页数:14
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