Anti-type II collagen antibody accelerates arthritis via CXCR2-expressing cells in IL-1 receptor antagonist-deficient mice.
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.
Kagari
Takashi
T
Biological Research Laboratories, Daiichi Sankyo Co Ltd, Tokyo, Japan. kagari.takashi.z4@daiichisankyo.co.jp
Tanaka
Daisuke
D
Doi
Hiromi
H
Iwakura
Yoichiro
Y
Shimozato
Takaichi
T
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000008:administration & dosage*; D024043:Collagen Type II / Q000276:immunology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000172:deficiency* / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis* / Q000235:genetics; D012720:Severity of Illness Index