Involvement of mannose-binding lectin in the pathogenesis of Kawasaki disease-like murine vasculitis.
Kawasaki disease (KD) is a paediatric idiopathic vasculitis. In this study, on the basis of studies using an established animal model for KD, we report that mannose-binding lectin (MBL) is involved in the pathogenesis of the disease. KD-like experimental murine vasculitis was induced by intraperitoneally administering a Candida albicans water-soluble extract (CAWS). MBL-A gradually increased in the serum of the model mice treated with CAWS. Deposition of MBL-A and MBL-C was observed in the aortic root, including the coronary arteries, which is a predilection site in experimental vasculitis. Corresponding to the distribution patterns of MBLs, marked deposition of C3/C3-derived peptides was also observed. Regarding the self-reactivity of MBLs, we observed that MBLs interacted with core histones to activate the lectin pathway. These results suggest that some types of pathogens provoke the MBL-dependent complement pathway (lectin pathway) to cause and/or exacerbate KD-like vasculitis.
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cyo, Hirokouji, Kawaramachi dori, Kamigyo-ku, Kyoto City 602-8566, Japan. Electronic address: nakam993@koto.kpu-m.ac.jp.
Akihiro
A
Nakamura
Department of Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cyo, Hirokouji, Kawaramachi dori, Kamigyo-ku, Kyoto City 602-8566, Japan.
Mitsuhiko
M
Okigaki
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Noriko
N
Miura
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cyo, Hirokouji, Kawaramachi dori, Kamigyo-ku, Kyoto City 602-8566, Japan.
Chinatsu
C
Suzuki
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Naohito
N
Ohno
Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
Fuyuki
F
Kametani
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cyo, Hirokouji, Kawaramachi dori, Kamigyo-ku, Kyoto City 602-8566, Japan.
Kenji
K
Hamaoka
D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D002176:Candida albicans / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology; D004195:Disease Models, Animal; D006657:Histones / Q000378:metabolism; D008297:Male; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D051379:Mice; D009080:Mucocutaneous Lymph Node Syndrome / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction
D000946:Antigens, Fungal; D006657:Histones; D037601:Mannose-Binding Lectin
Animal model; Kawasaki disease;; Mannose-binding lectin;; Vasculitis;