Arthritogenicity of collagen type II is increased by chlorination.
During inflammation, activated neutrophils, monocytes and macrophages produce and release myeloperoxidase (MPO). MPO converts hydrogen peroxide to hypochlorous acid, a highly reactive and oxidizing agent. Proteins subjected to hypochlorous acid become chlorinated. We analysed how chlorination of the cartilage antigen collagen type II (CII) affects its immunogenic and arthritogenic properties by studying immune responses to chlorinated CII in comparison to immune responses to CII and by studying the development of arthritis in rats immunized with CII-Cl. CII-Cl immunization of LEW.1AV1 rats caused a 100% incidence of arthritis with a mean maximum score of 9.2 (maximal score possible 16). The same dose of non-chlorinated CII did not induce arthritis at all. Rats immunized with CII-Cl developed high anti-CII-Cl IgG titres and also developed IgG antibodies recognizing the non-chlorinated form of CII. Analysis of cytokine mRNA expression in lymph nodes 10 days after immunzation revealed an increased expression of interferon (IFN)-gamma mRNA and interleukin (IL)-1beta mRNA in CII-Cl-immunized rats compared to CII-immunized rats. Thus, chlorination of CII increased its immunogenicity as well as its arthritogenicity. As neutrophils, monocytes and macrophages are abundant cells in arthritic joints of patients with rheumatoid arthritis, chlorination might be a mechanism by which immunoreactivity to CII is induced and by which chronic joint inflammation is supported.
Westman
E
E
Department of Medicine, Rheumatology unit, Karolinska Institutet, S-171 76 Stockholm, Sweden.
Lundberg
K
K
Erlandsson Harris
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H
D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000032:analysis; D002712:Chlorides / Q000378:metabolism; D024043:Collagen Type II / Q000009:adverse effects* / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000276:immunology
D001323:Autoantibodies; D002712:Chlorides; D024043:Collagen Type II; D007074:Immunoglobulin G; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D006997:Hypochlorous Acid; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D009195:Peroxidase