Vascular endothelium as a regulator of granulopoiesis: production of colony-stimulating activity by cultured human endothelial cells

Abstract

Colony-stimulating activity is a regulatory factor(s) that promotes differentiation of hemopoietic stem cells to mature granulocytes and macrophages; in man it has been found that blood monocytes, lymphocytes, and tissue macrophages produce it. In an effort to identify other potenitally physiologic tissue sources of colony-stimulating activity, we have studied the capacity of primary cultures of human vascular endothelial cells to produce colony-stimulating activity. Medium conditioned by incubation with endothelial cultures contained activity that promoted granulocyte-macrophage colony formation of nonadherent human and murine marrow cells. Exposure of endothelial cultures to 0.1-5.0 microgram/ml S. typhosa endotoxin for 6-72 hr enhanced colony-stimulating activity production. Similarly, incubation of endothelial cells with lysates of human blood granulocytes, or cocultivation with intact granulocytes, resulted in increased colony-stimulating activity levels. In 7-14 day cultures, freshly isolated endothelial cells, incorporated into agar underlayers, consistently stimulated more colony formation by nonadherent human marrow cells than comparable numbers of blood monocytes. These data indicate that: (1) cultured human endothelial cells are a potent source of colony-stimulating activity; (2) they respond to endotoxin and granulocytes and their contents by producing increased amounts of CSA; and (3) they produce morea colony-stimulating activity, than human blood monocytes under standardized conditions in vitro. These observations suggest that the vascular endothelium may play a role in the physiologic regulation of granulopoiesis.