Anti-type II collagen antibody accelerates arthritis via CXCR2-expressing cells in IL-1 receptor antagonist-deficient mice.

Abstract

Arthritis can be induced in mice by the injection of anti-type II collagen (anti-CII) Ab and LPS. To elucidate the role of IL-1 receptor antagonist (IL-1ra) in Ab-induced arthritis, WT and IL-1ra(-/-) mice were administered anti-CII Ab and LPS. These IL-1ra(-/-) mice developed severe arthritis even at low doses of anti-CII Ab and LPS, while WT mice did not. The cells that invaded the arthritic joints were mainly Gr-1(+) neutrophils, and the number of the cells in the joints remained high over 4 weeks in the IL-1ra(-/-) mice. KC, a ligand for CXCR2, is found in higher levels in the arthritic paws of IL-1ra(-/-) mice compared with the WT, and most of the cells that infiltrated into the joints of the IL-1ra(-/-) mice were CXCR2-expressing neutrophils. Administration of anti-CXCR2 Ab completely inhibited arthritis development. The anti-CXCR2 Ab decreased the number of neutrophils in the blood and also inhibited the migration of neutrophils to KC. These results suggested that the high susceptibility of IL-1ra(-/-) mice to anti-CII Ab-induced arthritis was due to the higher expression of chemotactic factors like KC and the sustained infiltration of CXCR2-expressing neutrophils into the joints.

• Authors: Takashi Kagari, Daisuke Tanaka, Hiromi Doi, Yoichiro Iwakura, Takaichi Shimozato
• Journal: European journal of immunology (Eur J Immunol) Vol. 37 Issue 10 Pg. 2753-63 (Oct 2007) ISSN: 0014-2980 [Print] Germany
• PMID: 17823985 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Collagen Type II
• Il1rn protein, mouse
• Interleukin 1 Receptor Antagonist Protein
• Lipopolysaccharides
• Receptors, Interleukin-8B

Topics

• Animals
• Arthritis, Experimental (immunology, pathology)
• Arthritis, Rheumatoid (immunology, pathology)
• Autoantibodies (administration & dosage)
• Collagen Type II (immunology)
• Interleukin 1 Receptor Antagonist Protein (deficiency, genetics)
• Lipopolysaccharides (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Neutrophils (immunology, metabolism)
• Receptors, Interleukin-8B (biosynthesis, genetics)
• Severity of Illness Index