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Effect of Kawasaki disease on migration of human umbilical vein endothelial cells
1Division of Pediatrics, Children's Research Hospital, Kyoto Prefectural University of Medicine, Japan.
Insights
Cytokines and anti-endothelial cell antibodies (AECA) in Kawasaki disease enhance endothelial cell migration, contributing to vasculitis. Intravenous gamma-globulin (IVGG) therapy effectively suppresses this migration, offering therapeutic benefits.
Area of Science:
- Immunology
- Vascular Biology
- Pediatric Rheumatology
Background:
- Kawasaki disease involves systemic vasculitis affecting coronary arteries in children.
- Immunoregulatory abnormalities, particularly involving endothelial cells, are implicated in its pathogenesis.
- Cytokines and anti-endothelial cell antibodies (AECA) are suspected contributors to vasculitis.
Purpose of the Study:
- To investigate the effects of specific cytokines and AECA on endothelial cell migration in Kawasaki disease.
- To determine the impact of intravenous gamma-globulin (IVGG) on cytokine- and AECA-induced endothelial cell migration.
Main Methods:
- Utilized a modified Boyden chamber assay to assess the migration of a human umbilical vein endothelial cell line (tHUE01).
- Examined the effects of interferon (IFN), IL-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, patient plasma, and rabbit AECA (rAECA) on cell migration.
- Assessed the influence of plasma from Kawasaki disease patients and IVGG-treated patients, as well as the effect of gamma-globulin addition.
Main Results:
- Plasma from acute Kawasaki disease patients significantly enhanced tHUE01 cell migration.
- Cytokines (except TNF-alpha) dose-dependently increased migration; anti-IFN antibody inhibited migration induced by IFN-gamma and patient plasma.
- rAECA stimulated migration, while plasma from IVGG-treated patients showed no effect; gamma-globulin inhibited cytokine- and rAECA-induced migration.
Conclusions:
- Cytokines and AECA play a role in Kawasaki disease vasculitis by promoting endothelial cell migration and potentially vessel wall damage.
- IVGG demonstrates therapeutic potential by suppressing endothelial cell migration, offering a mechanism for its effectiveness in treating Kawasaki disease.
Abstract:
Kawasaki disease, which is characterized by systemic vasculitis causing coronary arterial involvement in childhood, shows a variety of immunoregulatory abnormalities. Especially the direct or indirect deleterious effects on endothelial cells of cytokines and anti-endothelial cell antibodies (AECA) are considered to be involved in the mechanism responsible for production of vasculitis. Intravenous administration of high doses of gamma-globulin (IVGG) has been used as an effective therapy for Kawasaki disease. To examine the behavior of endothelial cells affected by cytokines and IVGG in Kawasaki disease, we studied the effects of interferon (IFN), IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha on the migration of human umbilical vein endothelial cell line (tHUE01) by a modified Boyden chamber method. Plasma from patients with acute Kawasaki disease markedly enhanced the migration of tHUE01 cells. Cytokines, with the exception of TNF-alpha, also enhanced the migration of tHUE01 cells in a dose-dependent manner. Anti-IFN antibody inhibited the migratory activity in response to not only IFN-gamma but also to the plasma from patients with Kawasaki disease. Rabbit AECA (rAECA) also significantly stimulated the migration of tHUE01 cells. Plasma from patients treated with IVGG did not affect the migration of tHUE01 cells. Addition of gamma-globulin significantly inhibited the migration of tHUE01 cells induced by the cytokines or rAECA. These results suggest that cytokines and AECA are important in restructuring and destroying vessel walls in Kawasaki disease by enhancing the migration of endothelial cells, and that IVGG may be therapeutically effective for this disease by suppressing this endothelial cell migration.