title: Temporal kinetics and cellular phenotype of TNF p55/p75 receptors in experimental allergic encephalomyelitis.
abstract: TNF-alpha and LT-alpha are thought to be involved in the immunopathology of CNS demyelinating diseases. Both cytokines induce cellular effects through 55-kDa type-1 receptors (R1) and 75-kDa type-2 receptors (R2). To date, no study has specifically identified the various cell populations that express TNF receptors (TNFR) in the inflammatory and demyelinating mouse model, EAE. Phenotyping the TNFR positive cells is important in determining when and where the ligands may be acting and playing a role in disease pathology. We observed an upregulation of TNF R1 and R2 mRNA in high endothelial venules (HEVs) in the lymph node and CNS before the onset of EAE (preclinical phase). This upregulation of TNFR expression in HEVs was followed by a rapid increase in leukocytes within the CNS after the onset of clinical disease. The temporal kinetics of these data suggest that HEVs become activated early, probably through the release of pro-inflammatory cytokines originating from circulating leukocytes. An increase in TNFR on HEVs would make these cells more susceptible to TNF-induced changes, such as increasing cellular adhesion molecules, thereby further facilitating the trafficking of leukocytes into the CNS parenchyma.
authors.affiliation: Mental Retardation Research Center, Department of Neurobiology, UCLA School of Medicine, Los Angeles, CA 90024-1759, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Kahn
authors.forename: J M
authors.initials: JM
authors.lastname: Dopp
authors.forename: S
authors.initials: S
authors.lastname: Liva
authors.forename: A J
authors.initials: AJ
authors.lastname: MacKenzie-Graham
authors.forename: R
authors.initials: R
authors.lastname: Chang
authors.forename: A
authors.initials: A
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Nazarian
authors.forename: P
authors.initials: P
authors.lastname: Dell'Albani
authors.forename: D
authors.initials: D
authors.lastname: Condorelli
authors.forename: R R
authors.initials: RR
authors.lastname: Voskuhl
authors.forename: J
authors.initials: J
authors.lastname: de Vellis
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D001399:Azure Stains; D015152:Blotting, Northern; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D007700:Kinetics; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology; D008214:Lymphocytes / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000737:chemistry / Q000276:immunology; D009000:Monocytes / Q000737:chemistry / Q000276:immunology; D009504:Neutrophils / Q000737:chemistry / Q000276:immunology; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012008:Recurrence; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D001399:Azure Stains; D015347:RNA Probes; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D019696:Peptidylprolyl Isomerase