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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
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Fibronectin- and vitronectin-induced microglial activation and matrix metalloproteinase-9 expression is mediated by

Richard Milner1, Stephen J Crocker, Stephanie Hung

  • 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, 20550 North Torrey Pines Road, La Jolla, CA 92037, USA. rmilner@scripps.edu

Journal of Immunology (Baltimore, Md. : 1950)
|June 6, 2007
PubMed

Insights

Plasma proteins fibronectin and vitronectin promote microglial activation in multiple sclerosis models. This study reveals their role in demyelinating disease pathogenesis via alpha(5)beta(1) and alpha(v)beta(5) integrins.

Area of Science:

  • Neuroimmunology
  • Cellular and Molecular Neuroscience

Background:

  • Multiple sclerosis involves blood-brain barrier compromise, allowing plasma proteins like fibronectin and vitronectin into the brain.
  • Previous in vitro studies indicated fibronectin and vitronectin promote microglial activation.

Purpose of the Study:

  • To investigate the in vivo role of fibronectin and vitronectin in modulating microglial activation during demyelinating disease.
  • To explore the specific integrin pathways involved in fibronectin and vitronectin-mediated microglial responses.

Main Methods:

  • Utilized an experimental autoimmune encephalomyelitis mouse model for demyelination.
  • Assessed fibronectin and vitronectin levels, microglial activation, and matrix metalloproteinase-9 expression in brain tissue.
  • Employed murine cell culture with flow cytometry and gelatin zymography to analyze microglial responses.
  • Conducted function-blocking studies using specific integrins.

Main Results:

  • Elevated brain fibronectin and vitronectin levels correlated with microglial activation and matrix metalloproteinase-9 expression in the disease model.
  • Fibronectin and vitronectin significantly increased microglial activation and pro-matrix metalloproteinase-9 expression in cell culture.
  • The effects of fibronectin and vitronectin were mediated by alpha(5)beta(1) and alpha(v)beta(5) integrins, respectively.

Conclusions:

  • Fibronectin and vitronectin deposition during demyelinating disease influences microglial activation states.
  • Alpha(5)beta(1) and alpha(v)beta(5) integrins are key mediators of microglial activation induced by fibronectin and vitronectin.

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