EFFECT OF KAWASAKI-DISEASE ON MIGRATION OF HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

Kawasaki disease, which is characterized by systemic vasculitis causin g coronary arterial involvement in childhood, shows a variety of immun oregulatory abnormalities. Especially the direct or indirect deleterio us effects on endothelial cells of cytokines and anti-endothelial cell antibodies (AECA) are considered to be involved in the mechanism resp onsible for production of vasculitis. Intravenous administration of hi gh doses of gamma-globulin (IVGG) has been used as an effective therap y for Kawasaki disease. To examine the behavior of endothelial cells a ffected by cytokines and IVGG in Kawasaki disease, we studied the effe cts of interferon (IFN), IL-1 beta, IL-6, and tumor necrosis factor (T NF)-alpha on the migration of human umbilical vein endothelial cell li ne (tHUEO1) 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-cr, also enhanced the migr ation of tHUEO1 cells in a dose-dependent manner. Anti-IFN antibody in hibited the migratory activity in response to not only IFN-gamma but a lso to the plasma from patients with Kawasaki disease. Rabbit AECA (rA ECA) also significantly stimulated the migration of tHUEO1 cells. Plas ma from patients treated with IVGG did not affect the migration of tHU EO1 cells. Addition of y-globuIin significantly inhibited the migratio n of tHUEO1 cells induced by the cytokines or rAECA. These results sug gest that cytokines and AECA are important in restructuring and destro ying vessel walls in Kawasaki disease by enhancing the migration of en dothelial cells, and that IVGG may be therapeutically effective for th is disease by suppressing this endotheliaI cell migration.