Microglial expression of alphavbeta3 and alphavbeta5 integrins is regulated by cytokines and the extracellular matrix: beta5 integrin null microglia show no defects in adhesion or MMP-9 expression on vitronectin
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Updated: Jun 28, 2026

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
1Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. rmilner@scripps.edu
Abstract:
As the primary immune effector cells in the CNS, microglia play a central role in regulating inflammation. The extracellular matrix (ECM) protein vitronectin is a strong inducer of microglial activation, switching microglia from a resting into an activated potentially destructive phenotype. As the activating effect of vitronectin is mediated by alphav integrins, the aim of the current study was to evaluate the requirement of the alphavbeta5 integrin in mediating microglial adhesion and activation to vitronectin, by studying these events in beta5 integrin-null murine microglia. Surprisingly, beta5 integrin null microglia were not defective in adhesion to vitronectin. Further analysis showed that microglia express the alphavbeta3 integrin, in addition to alphavbeta5. Flow cytometry revealed that microglial alphav integrin expression is regulated by cytokines and ECM proteins. alphavbeta3 integrin expression was downregulated by IFN-gamma, TNF, LPS, and TGF-beta1. alphavbeta5 expression was also reduced by IFN-gamma, TNF, and LPS, but strongly increased by the antiactivating factors TGF-beta1 and laminin. Gel zymography revealed that beta5 integrin null microglia showed no deficiency in their expression of matrix metalloproteinase (MMP)-9 in response to vitronectin. Taken together, these data show that microglia express two different alphav integrins, alphavbeta3 and alphavbeta5, and that expression of these integrins is independently regulated by cytokines and ECM proteins. Furthermore, it reveals that the alphavbeta5 integrin is not essential for mediating microglial adhesion and MMP-9 expression in response to vitronectin.
Insights
Microglia utilize both alphavbeta3 and alphavbeta5 integrins for activation. The alphavbeta5 integrin is not essential for microglial adhesion or matrix metalloproteinase-9 expression when responding to vitronectin.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Extracellular Matrix Biology
Background:
- Microglia are key immune cells in the central nervous system (CNS), regulating inflammation.
- The extracellular matrix (ECM) protein vitronectin activates microglia, shifting them to a potentially destructive phenotype.
- Vitronectin's activating effect is mediated by alphav integrins.
Purpose of the Study:
- To investigate the role of the alphavbeta5 integrin in microglial adhesion and activation by vitronectin.
- To analyze microglial responses in beta5 integrin-null murine models.
Main Methods:
- Utilized beta5 integrin-null murine microglia for adhesion and activation assays.
- Employed flow cytometry to analyze alphav integrin expression.
- Performed gel zymography to assess matrix metalloproteinase-9 (MMP-9) expression.
Main Results:
- Beta5 integrin-null microglia showed no defect in adhesion to vitronectin.
- Microglia express both alphavbeta3 and alphavbeta5 integrins.
- Cytokines and ECM proteins differentially regulate alphavbeta3 and alphavbeta5 integrin expression.
- Alphavbeta5 integrin-null microglia exhibited normal MMP-9 expression in response to vitronectin.
Conclusions:
- Microglia express both alphavbeta3 and alphavbeta5 integrins, with independently regulated expression patterns.
- The alphavbeta5 integrin is not essential for vitronectin-mediated microglial adhesion and MMP-9 expression.
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