Role of Anti-Endothelial Cell Antibody in the Development of Coronary Arterial Lesions in Kawasaki Disease
Korean Circulation Journal
; : 723-731, 2006.
Article
em Ko
| WPRIM
| ID: wpr-197993
Biblioteca responsável:
WPRO
ABSTRACT
BACKGROUND AND OBJECTIVES : Anti-endothelial cell antibodies (AECA) are found in the sera of many patients with Kawasaki disease (KD). In this study, the pathogenic role of AECA in the development of coronary arterial lesions of KD was investigated. SUBJECTS AND METHODS : Serum IgM-AECA concentrations were measured in 22 KD patients. Cultured human coronary artery endothelial cells (HCAEC) were incubated with either acute or convalescent phase sera, and their expressions of intercellular adhesion molecule-1 (ICAM-1) assessed. IgM fractions of the sera were purified, and their ability to induce ICAM-1 mRNA and protein expressions evaluated. To address the signal transduction pathways involved in IgM-AECA-induced ICAM-1 expression, the blocking effect of four protein kinase inhibitors, PD98059, SB203580, dimethylaminopurine (DMAP) and parthenolide were measured. RESULTS : IgM-AECA was present in 14 out of 22 (64%) acute KD sera. ICAM-1 expression of HCAEC incubated with acute KD sera (117.1+/-46.7) and AECA-positive acute KD sera (143.3+/-37.5) were significantly higher than those of the convalescent KD sera (88.9+/-14.4, p<0.05) or AECA-negative acute KD sera (71.2+/-11.8, p<0.05), respectively. IgM-AECA from KD patients significantly induced ICAM-1 protein and mRNA expression. The upregulation of ICAM-1 expression was significantly inhibited by SB203580, DMAP and parthenolide, but not by PD98059. CONCLUSION : IgM-AECA was detected in the sera of about 2/3 of acute KD patients, which activated endothelial cells by upregulation of ICAM-1 expression, possibly via p38, JNK MAPK and NF-kappaB signal transduction pathways. Thus, IgM-AECA may play a pathogenic role in the development of coronary arterial lesions in KD patients.
Palavras-chave
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Imunoglobulina M
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RNA Mensageiro
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Transdução de Sinais
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Regulação para Cima
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NF-kappa B
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Molécula 1 de Adesão Intercelular
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Anomalias dos Vasos Coronários
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Vasos Coronários
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Células Endoteliais
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Inibidores de Proteínas Quinases
Limite:
Humans
Idioma:
Ko
Revista:
Korean Circulation Journal
Ano de publicação:
2006
Tipo de documento:
Article