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The FASEB Journal, Vol 9, 1605-1613, Copyright © 1995 by The Federation of American Societies for Experimental Biology


RESEARCH COMMUNICATIONS

Vitronectin overrides a negative effect of TNF-alpha on astrocyte migration

A Faber-Elman, V Lavie, I Schvartz, S Shaltiel and M Schwartz
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Morphogenesis and tissue repair require appropriate cross-talk between the cells and their surrounding milieu, which includes extracellular components and soluble factors, e.g., cytokines and growth factors. The present work deals with this communication needed for recovery after axotomy in the central nervous system (CNS). The failure of CNS axons to regenerate after axonal injury has been attributed, in part, to astrocyte failure to repopulate the injury site. The goal of this work was to provide an in vitro model to mimic the in vivo response of astrocytes to nerve injury and to find ways to modulate this response and create a milieu that favors astrocyte migration and repopulation of the injury site. In an astrocyte scratch wound model, we blocked astrocyte migration by tumor necrosis factor alpha (TNF-alpha). This effect could not be reversed by astrocyte migration-inducing factors such as transforming growth factor beta 1 (TGF-beta 1) or by any of the tested extracellular matrix (ECM) components (laminin and fibronectin) except for vitronectin (Vn). Vn, added together with TNF-alpha, counteracted the TNF-alpha blockage and allowed a massive migration of astrocytes (not due to cell proliferation) beyond that allowed by Vn only. Heparan sulfate proteoglycans (HSPG) were shown to be involved in the migration. The results may be relevant to regeneration of CNS axons, and may also provide an example that an extracellular component (Vn) can overcome and neutralize a negative effect of a growth factor/cytokine (TNF-alpha) and can act in synergy with other features of this cytokine to promote a necessary function (e.g., cell migration) that is otherwise inhibited.


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T. Lefrancois, C. Fages, M. Peschanski, and M. Tardy
Neuritic Outgrowth Associated with Astroglial Phenotypic Changes Induced by Antisense Glial Fibrillary Acidic Protein (GFAP) mRNA in Injured Neuron-Astrocyte Cocultures
J. Neurosci., June 1, 1997; 17(11): 4121 - 4128.
[Abstract] [Full Text] [PDF]




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Copyright © 1995 by The Federation of American Societies for Experimental Biology.