title: Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production.
abstract: Although considered an immunologically privileged site, the central nervous system (CNS) can display significant inflammatory responses, which may play a pathogenic role in a number of neurological diseases. Microglia appear to be particularly important for initiating and sustaining CNS inflammation. These cells exist in a quiescent form in the normal CNS, but acquire macrophage-like properties (including active phagocytosis, upregulation of proteins necessary for antigen presentation, and production of proinflammatory cytokines) after stimulation with inflammatory substances such as lipopolysaccharide (LPS). Recent studies have focused on elucidating the role of neurons in the regulation of microglial inflammatory responses. In the present study, we demonstrate, using neuron-microglial cocultures, that neurons are capable of inhibiting LPS-induced tumor necrosis factor-alpha (TNF-alpha) production by microglia. This inhibition appears to be dependent on secretion of substances at axon terminals, as treatment with the presynaptic calcium channel blocker omega-conotoxin abolishes this inhibitory effect. Moreover, we show that conditioned medium from neuronal cultures similarly inhibits microglial TNF-alpha production, which provides additional evidence that neurons secrete inhibitory substances. We previously demonstrated that the transmembrane protein-tyrosine phosphatase CD45 plays an important role in negatively regulating microglial activation. The recent characterization of CD22 as an endogenous ligand of this receptor led us to investigate whether neurons express this protein. Indeed, we were able to demonstrate CD22 mRNA and protein expression in cultured neurons and mouse brain, using reverse transcriptase-polymerase chain reaction and antibody-based techniques. Furthermore, we show that neurons secrete CD22, which functions as an inhibitor of microglial proinflammatory cytokine production.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Mott
authors.forename: Ghania
authors.initials: G
authors.lastname: Ait-Ghezala
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
authors.forename: Takashi
authors.initials: T
authors.lastname: Mori
authors.forename: Martina
authors.initials: M
authors.lastname: Vendrame
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.forename: Jared
authors.initials: J
authors.lastname: Ehrhart
authors.forename: Michae
authors.initials: M
authors.lastname: Mullan
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015815:Cell Adhesion Molecules; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000276:immunology; D037102:Lectins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D002121:Calcium Channel Blockers; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D016207:Cytokines; D037102:Lectins; D008024:Ligands; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051918:Sialic Acid Binding Ig-like Lectin 2; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens