Granulocyte interactions with GM-CSF and G-CSF secretion by endothelial cells and monocytes

We have, in previous studies, characterized the cytokine and cellular regul ation of GM-CSF and G-CSF production by monocytes and endothelial cells. In this study, we investigated the regulatory role of granulocytes, The addit ion of granulocytes to endotoxin-stimulated monocytes dose-dependently decr eased both GM-CSF and G-CSF concentrations, presumably by absorbing the cyt okines, A similar dose-dependent decrease in GM-CSF concentration was found when granulocytes were added to IL-1-stimulated endothelial cells. In cont rast, G-CSF secretion by endothelial cells responded to granulocytes in a b iphasic fashion. At low granulocyte concentrations, endothelial cells respo nded with an increased G-CSF secretion, but at high concentrations of granu locytes G-CSF secretion was down modulated. Our results suggest that there exist two loops between granulocytes and endothelial cells for regulating G -CSF activity. Granulocytes can stimulate G-CSF secretion by activated endo thelial cells but can also decrease the biological activity by absorbing th e cytokine, These mechanisms might be involved in the regulation of the loc al and systemic levels of granulocytes.