Effect of Kawasaki Disease on Migration of Human Umbilical Vein Endothelial Cells

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.