Effect of various agents and physical damage on giant cell formation in bovine aortic endothelial cell cultures

Abstract

Giant bovine aortic endothelial cells (mononucleated and multinucleated), morphologically identical to cells previously described in situ in damaged vessel walls and in various diseased states, can be increased in numbers in culture by treatment with 1 × 10 −6 M epinephrine, 1 × 10 −6 M nicotine sulfate, 1.2 × 10 −6 M 7-ketocholesterol, or 1 × 10 −8 M β-estradiol. Lower levels of epinephrine (1 × 10 −9 and 1 × 10 −12 M) decreased the rate of giant cell formation but had little effect on the number found in cultures at confluency when compared with 10 −6 M epinephrine. However, 1 × 10 −6 M serotonin suppressed the formation of giant cells. Cells scraped from confluent monolayers of normal endothelial cell cultures are replaced with the denuded area by giant endothelial cells. Cultures treated daily for 5 days with epinephrine, 7-ketocholesterol, nicotine sulfate, and β-estradiol contained large nonrandom patches of giant cells at confluency. Within 1 to 2 days after cultures reached confluency, giant cells underwent necrosis and apparent cell death, leaving sparse or denuded areas in the confluent monolayers sheets. Treatment of such cultures with bovine platelets resulted in the interaction of platelets with an extensive meshwork of exposed microfibrillar material within these holes. These results demonstrate that normal bovine aortic endothelial cells in culture can be induced under restricted experimental conditions to undergo morphological changes. Such conditions and the resulting formation of giant endothelial cells are consistent with those which give rise to giant endothelial cells in vivo. This investigation suggests that endothelial cell cultures could be a useful model for the study of the pathogenesis of various vascular disease states.