Open AccessLectin‐like oxidized low‐density lipoprotein receptor 1 mediates leukocyte infiltration and articular cartilage destruction in rat zymosan‐induced arthritis
Author(s) -
Nakagawa Takefumi,
Akagi Masao,
Hoshikawa Hajime,
Chen Mingyi,
Yasuda Tadashi,
Mukai Shogo,
Ohsawa Kunitaka,
Masaki Tomoh,
Nakamura Takashi,
Sawamura Tatsuya
Publication year - 2002
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.10504
Subject(s) - arthritis , synovitis , inflammation , proinflammatory cytokine , zymosan , cartilage , medicine , immunology , infiltration (hvac) , rheumatoid arthritis , synovial fluid , cellular infiltration , pathology , osteoarthritis , chemistry , anatomy , biochemistry , physics , alternative medicine , in vitro , thermodynamics
Objective The relationship between rheumatoid arthritis and atherosclerosis has been recognized for >20 years. This study aimed to elucidate the roles of oxidized low‐density lipoprotein (ox‐LDL; one of the main pathogenic factors of atherosclerosis) and its endothelial receptor, lectin‐like ox‐LDL receptor 1 (LOX‐1), in arthritic joints using a rat zymosan‐induced arthritis (ZIA) model. Methods LOX‐1 expression and ox‐LDL accumulation in arthritic joints were detected by immunohistochemistry using specific mouse anti–LOX‐1 and anti–ox‐LDL monoclonal antibodies, respectively. To elucidate the effects of the expressed LOX‐1 on arthritis, ZIA rats were treated with anti–LOX‐1 antibody or normal mouse IgG. The severity of arthritis was analyzed by joint swelling. Cell infiltration, synovial hyperplasia, and proteoglycan losses were also determined by histologic scoring. Proinflammatory cytokine and nitrite levels in serum and joint fluid were also measured. Results Immunohistochemical study of ZIA demonstrated LOX‐1 expression on synovial endothelium and postcapillary venules at 6 hours after the induction of inflammation, with maximum expression detected at 24 hours. LOX‐1 was also expressed weakly on both joint cartilage and synovium. Ox‐LDL, a ligand of LOX‐1, was also detected in articular chondrocytes. Administration of anti–LOX‐1 antibody, which blocks LOX‐1 activity, suppressed joint swelling (by 33.5%), leukocyte infiltration, and joint nitrite accumulation at 24 hours, as well as cartilage destruction at 7 days, compared with control rats. Conclusion LOX‐1 induction in arthritic joints might play a role in promoting joint inflammation and cartilage destruction by mediating leukocyte infiltration into the arthritic joints of ZIA rats.