P2Y12 expression and function in alternatively activated human microglia

Moore, Craig S. and Ase, Ariel R. and Kinsara, Angham and Rao, Vijayaraghava T.S. and Michell-Robinson, Mackenzie and Leong, Soo Yuen and Butovsky, Oleg and Ludwin, Samuel K. and Séguéla, Philippe and Bar-Or, Amit and Antel, Jack P. (2015) P2Y12 expression and function in alternatively activated human microglia. Neurology: Neuroimmunology and Neuroinflammation, 2 (2). ISSN 2332-7812

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Abstract

Objective: To investigate and measure the functional significance of altered P2Y12 expression in the context of human microglia activation. Methods: We performed in vitro and in situ experiments to measure how P2Y12 expression can influence disease-relevant functional properties of classically activated (M1) and alternatively activated (M2) human microglia in the inflamed brain. Results: We demonstrated that compared to resting and classically activated (M1) human microglia, P2Y12 expression is increased under alternatively activated (M2) conditions. In response to ADP, the endogenous ligand of P2Y12, M2 microglia have increased ligand-mediated calcium responses, which are blocked by selective P2Y12 antagonism. P2Y12 antagonism was also shown to decrease migratory and inflammatory responses in human microglia upon exposure to nucleotides that are released during CNS injury; no effects were observed in human monocytes or macrophages. In situ experiments confirm that P2Y12 is selectively expressed on human microglia and elevated under neuropathologic conditions that promote Th2 responses, such as parasitic CNS infection. Conclusion: These findings provide insight into the roles of M2 microglia in the context of neuroinflammation and suggest a mechanism to selectively target a functionally unique population of myeloid cells in the CNS.

Item Type: Article
URI: http://research.library.mun.ca/id/eprint/11805
Item ID: 11805
Additional Information: Memorial University Open Access Author's Fund. CORRECTION P2Y12 expression and function in alternatively activated human microglia. In the article “P2Y12 expression and function in alternatively activated human microglia” by C.S. Moore et al. (Neurology® Neuroimmunology & Neuroinflammation 2015;2:e80), there is an error in figure 6, panel C, first image. The image should have been titled CD163. The editorial staff regrets the error.
Department(s): Medicine, Faculty of > Biomedical Sciences
Date: 19 March 2015
Date Type: Publication
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