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Fibronectin- and vitronectin-induced microglial activation and matrix metalloproteinase-9 expression is mediated by integrins alpha(5)beta(1) and alpha(v)beta(5)

Academic Article
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Overview

authors

  • Milner, Richard
  • Crocker, S. J.
  • Hung, S.
  • Wang, X. Y.
  • Frausto, R. F.
  • del Zoppo, G. J.

publication date

  • June 2007

journal

  • Journal of Immunology  Journal

abstract

  • Early in the pathogenesis of multiple sclerosis, the blood-brain barrier is compromised, which leads to deposition of the plasma proteins fibronectin and vitronectin in cerebral parenchyma. In light of our previous finding that microglial activation in vitro is strongly promoted by fibronectin and vitronectin, we set out to examine the possibility that modulation of microglial activation by fibronectin or vitronectin is an important regulatory mechanism in vivo. In an experimental autoimmune encephalomyelitis mouse model of demyelination, total brain levels of fibronectin and vitronectin were strongly increased and there was a close relationship between fibronectin and vitronectin deposition, microglial activation, and microglial expression of matrix metalloproteinase-9. In murine cell culture, flow cytometry for MHC class I and gelatin zymography revealed that microglial activation and expression of pro-matrix metalloproteinase-9 were significantly increased by fibronectin and vitronectin. Function-blocking studies showed that the influence of fibronectin and vitronectin was mediated by the alpha(5)beta(1) and alpha(v)beta(5) integrins, respectively. Taken together, this work suggests that fibronectin and vitronectin deposition during demyelinating disease is an important influence on microglial activation state. Furthermore, it provides the first evidence that the alpha(5)beta(1) and alpha(v)beta(5) integrins are important mediators of microglial activation.

subject areas

  • Animals
  • Brain
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental
  • Enzyme Precursors
  • Fibronectins
  • Histocompatibility Antigens Class I
  • Integrin alpha5beta1
  • Integrins
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred C57BL
  • Microglia
  • Receptors, Vitronectin
  • Vitronectin
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 17548654
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Additional Document Info

start page

  • 8158

end page

  • 8167

volume

  • 178

issue

  • 12

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