Human vascular endothelial cells, granulopoiesis, and the inflammatory response

We have carried out a series of in vitro studies designed to characterize the role of mononuclear phagocytes as regulators of hematopoiesis. The results of these studies have demonstrated that mononuclear phagocytes produce factors, including interleukin-1 (IL-1), that induce the expression of multilineage hematopoietic growth factors by human vascular endothelial cells. In more recent studies we and others have identified these induced factors as G-CSF, GM-CSF, IL-6, and IL-1. Interleukin 1 stimulates expression of these genes by inducing the accumulation of gene transcripts. Moreover, transcript accumulation, at least with GM-CSF, results from prolongation of mRNA half-life. Based on preliminary studies in a cell-free system, we propose that the inductive capacity of IL-1 results from its activation of ribonuclease inhibitors in the cytoplasm of IL-1-induced cells and hypothesize that this may be a general mechanism by which IL-1 induces gene expression.