Growth-promoting actions of extracts from mouse submaxillary glands on human endothelial cells in culture

Extracts of submaxillary glands from two different strains of inbred mice were mitogenic for human endothelial cells in culture. The mitogenic activity of extracts from glands of males of the SWR/J and C57BL/10J strains were equivalent, and the growth stimulating effect was unrelated to renin or esteroproteolytic activity. Mitogenic activity in extracts from SWR/J females was less than that from males, and extracts from C57BL/10J females were inactive. The polypeptide growth factors, epidermal (EGF) and fibroblast (FGF) growth factors, also stimulated replication of endothelial cells. Cells from either umbilical arteries or veins responded to submaxillary extracts, EGF, or FGF with a similar increase in cell number, increase in protein and enhanced uptake of 3H-thymidine. The proliferative response was associated with decreased activity of angiotensin I converting enzyme which is localized on the endothelial surface. Nerve growth factor (NGF) was not mitogenic for endothelial cells. Extracts of submaxillary glands from male mice of either strain contained approximately 20 times more EGF than extracts from females, as determined by immunodiffusion. Mitogenic activity of the extracts was completely inhibited by antiserum to EGF, suggesting that the active component of these preparations is EGF.