title: Expression and function of junctional adhesion molecule-C in human and experimental arthritis.
abstract: Junctional adhesion molecule-C (JAM-C) is an adhesion molecule involved in transendothelial migration of leukocytes. In this study, we examined JAM-C expression in the synovium and investigated the role of this molecule in two experimental mouse models of arthritis. JAM-C expression was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of a monoclonal anti-JAM-C antibody were assessed in antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis. JAM-C was expressed by synovial fibroblasts in the lining layer and associated with vessels in the sublining layer in human and mouse arthritic synovial tissue. In human tissue, JAM-C expression was increased in rheumatoid arthritis (RA) as compared to osteoarthritis synovial samples (12.7 +/- 1.3 arbitrary units in RA versus 3.3 +/- 1.1 in OA; p < 0.05). Treatment of mice with a monoclonal anti-JAM-C antibody decreased the severity of AIA. Neutrophil infiltration into inflamed joints was selectively reduced as compared to T-lymphocyte and macrophage infiltration (0.8 +/- 0.3 arbitrary units in anti-JAM-C-treated versus 2.3 +/- 0.6 in isotype-matched control antibody-treated mice; p < 0.05). Circulating levels of the acute-phase protein serum amyloid A as well as antigen-specific and concanavalin A-induced spleen T-cell responses were significantly decreased in anti-JAM-C antibody-treated mice. In the serum transfer-induced arthritis model, treatment with the anti-JAM-C antibody delayed the onset of arthritis. JAM-C is highly expressed by synovial fibroblasts in RA. Treatment of mice with an anti-JAM-C antibody significantly reduced the severity of AIA and delayed the onset of serum transfer-induced arthritis, suggesting a role for JAM-C in the pathogenesis of arthritis.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University Hospital, 26 avenue Beau-Séjour, 1211 Geneva 14, Switzerland.
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
authors.forename: Michel
authors.initials: M
authors.lastname: Aurrand-Lions
authors.forename: Dominique
authors.initials: D
authors.lastname: Talabot-Ayer
authors.forename: Véronique
authors.initials: V
authors.lastname: Chobaz-Péclat
authors.forename: Claudia
authors.initials: C
authors.lastname: Zimmerli
authors.forename: Philippe
authors.initials: P
authors.lastname: Hammel
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000032:analysis; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C448000:JAM3 protein, human; C486723:Jam3 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein