Microglial expression of αvβ3 and αvβ5 integrins is regulated by cytokines and the extracellular matrix: β5 integrin null microglia show no defects in adheison or MMP-9 expression on vitronectin

摘要

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 αv integrins, the aim of the current study was to evaluate the requirement of the αvβ5 integrin in mediating microglial adhesion and activation to vitronectin, by studying these events in β5 integrin-null murine microglia. Surprisingly, β5 integrin null microglia were not defective in adhesion to vitronectin. Further analysis showed that microglia express the αvβ3 integrin, in addition to αvβ5. Flow cytometry revealed that microglial av integrin expression is regulated by cytokines and ECM proteins. αvβ3 integrin expression was downregulated by IFN-γ, TNF, LPS, and TGF-β1. αvβ5 expression was also reduced by IFN-γ, TNF, and LPS, but strongly increased by the antiactivating factors TGF-β1 and laminin. Gel zymography revealed that β5 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 αv integrins, αvβ3 and αvβ5, and that expression of these integrins is independently regulated by cytokines and ECM proteins. Furthermore, it reveals that the αvβ5 integrin is not essential for mediating microglial adhesion and MMP-9 expression in response to vitronectin.