Endothelial cells regulate the proliferation of monocytes in vitro

Monocytes (MΦs) are among the first cells to accumulate in early atherosclerotic lesions and generally are believed to be incapable of proliferation. However, recent studies indicate that the number of MΦs in atherosclerotic lesion may increase due to induction of local proliferation. Since proliferation of hematopoietic lineage cells is strongly influenced by interaction with neighboring cell types, we examined the ability of vascular endothelial cells (EC), smooth muscle cells or fibroblasts to stimulate MΦ proliferation. In this study, we show that only when seeded at high densities MΦs could proliferate in culture. However, when contact co-cultured with EC, MΦs proliferated at a higher rate (260% on day 6) than those cultured alone or co-cultured with smooth muscle cells or fibroblasts. Endothelial cells could stimulate the proliferation of MΦs even at non-proliferating densities. Only EC that were growth arrested or in lag phase could induce MΦ proliferation, whereas those in the exponential proliferating phase were non-stimulatory. Conditioned medium prepared from EC in growth arrested or lag phase failed to stimulate MΦ proliferation. Similarly physical separation of MΦs from EC also resulted in no proliferation. These results suggest that EC induced MΦ proliferation is contact dependent and no soluble factors are involved in this induction. This EC induced MΦ proliferation may have a profound effect on the rate of progression of atherosclerosis.