Lectin-like oxidized low-density lipoprotein receptor 1 mediates leukocyte infiltration and articular cartilage destruction in rat zymosan-induced arthritis

Takefumi Nakagawa, Masao Akagi, Hajime Hoshikawa, Mingyi Chen, Tadashi Yasuda, Shogo Mukai, Kunitaka Ohsawa, Tomoh Masaki, Takashi Nakamura, Tatsuya Sawamura

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

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 antiox-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.

Original languageEnglish (US)
Pages (from-to)2486-2494
Number of pages9
JournalArthritis and rheumatism
Volume46
Issue number9
DOIs
StatePublished - Sep 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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