Resident microglia from adult mice are refractory to nitric oxide-inducing stimuli due to impaired NOS2 gene expression

Glia
Courtney A Brannan, Margo R Roberts

Abstract

Microglia are the immunoregulatory cells of the central nervous system (CNS) and share many characteristics with resident macrophages in extracerebral tissues. Nitric oxide (NO) is secreted by macrophages following induction of the NO synthase gene NOS2 by stimuli elicited during a T-cell response and/or by microbial products. NO regulates both innate and adaptive immune responses, such as killing intracellular pathogens and inhibiting T-cell proliferation. Regulation of NO production by microglia, however, is poorly understood. We find that microglia from healthy adult mice produce negligible amounts of NO compared with resident macrophages during restimulation of peptide-specific CD8 T cells, and therefore cannot block T-cell proliferation. The impaired NO response extends to exogenous NOS2-inducing stimuli, including cytokines, CD40 ligation, and lipopolysaccharide. In contrast, microglia produce proinflammatory cytokines in response to these same stimuli, and therefore possess a relatively selective block in NO production. We go on to show that resident microglia fail to produce detectable levels of either the NOS2 enzyme or NOS2 RNA in response to NO-inducing stimuli. We therefore propose that microglia in the healthy adul...Continue Reading

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Citations

Aug 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·C A ColtonH Dawson
Jul 4, 2012·Neurosurgery Clinics of North America·Seunggu J HanAndrew T Parsa
Jan 26, 2010·Journal of Neuroscience Methods·Simon Moussaud, Henning Joerg Draheim
Dec 1, 2009·Neurosurgery Clinics of North America·Seunggu J HanMichael Lim
Dec 1, 2009·Neurosurgery Clinics of North America·Gurvinder KaurCourtney Crane
Nov 21, 2009·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Isaac YangAndrew T Parsa
Jul 15, 2009·Journal of Neuroscience Methods·Ping K YipMarzia Malcangio
Jan 10, 2012·Experimental Neurology·Dominic Schomberg, Julie K Olson

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