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

摘要: Microglia are the immunoregulatory cells of central nervous system (CNS) and share many characteristics with resident macrophages in extracerebral tissues. Nitric oxide (NO) is secreted by following induction NO synthase gene NOS2 stimuli elicited during a T-cell response and/or microbial products. regulates both innate adaptive immune responses, such as killing intracellular pathogens inhibiting proliferation. Regulation production microglia, however, poorly understood. We find that microglia from healthy adult mice produce negligible amounts compared restimulation peptide-specific CD8 T cells, therefore cannot block The impaired extends to exogenous NOS2-inducing stimuli, including cytokines, CD40 ligation, lipopolysaccharide. In contrast, proinflammatory cytokines these same possess relatively selective production. go on show fail detectable levels either enzyme or RNA NO-inducing stimuli. propose brain exist an “NO-incompetent” state which blocked at level RNA. inability CNS may allow modulate processes temporally, serve protect irreparable damage onset infection injury. © 2004 Wiley-Liss, Inc.