Induction of giant endothelial cells in culture by K-252a, a protein kinase inhibitor.

K-252a, a protein kinase inhibitor with a wide spectrum of activity, inhibited the serum-stimulated proliferation of cultured bovine carotid endothelial cells dose-dependently, and all the cells became remarkably large, with a diameter of more than 150 microns at K-252a concentrations of 0.3-1 microgram/ml. This effect of the agent was reproducible under the conditions described in this article. When the endothelial cells became abnormally large by K-252a, the surface area of the cell became wider, and the F-actin molecules increased in both number and length. Despite their abnormal size, K-252a-induced giant cells maintained at least three physiological functions characteristic to normal endothelial cells: 1) ability to take up acetylated low density lipoprotein, 2) ability to produce and secrete endothelin and 3) ability to respond via an increase of [Ca2+]i to the stimulation by bradykinin. These observations suggest that K-252a-induced giant cells are useful tools for examining the function of endothelial cells because it is very reproducible and can be produced by an easy treatment.