Human colony-stimulating factors and stromal cell function.

Abstract

Hematopoiesis and the function of mature blood cells are linked by the CSFs, a class of distinct glycoproteins that have considerable overlap in their actions, tissue sources, and production by cells in response to different inducing agents. These relationships are most evident when the system is stimulated in response to exogenous agents. Monocytes may lie at the center of this response, as LPS induces the release of GM-CSF and G-CSF, as well as the monokines IL-1 and TNF. GM-CSF and G-CSF act on mature cells at the site of inflammation, increasing their functional capacity by concentration-dependent effects on chemotaxis, increased phagocytosis, enhanced superoxide production, and increased antibody-dependent cellular cytotoxicity (Vadas et al., 1983a, b; Gasson et al., 1984; Weisbart et al., 1985). The release by monocytes of IL-1 and TNF may amplify this response by inducing local fibroblasts and endothelial cells to produce more GM-CSF and G-CSF. The release of GM-CSF and G-CSF into the circulation could increase bone marrow granulocyte production. Increased circulating levels of IL-1 and/or TNF would also be expected to increase bone marrow stromal cell production of GM-CSF and G-CSF. In conjunction with foreign antigen, IL-1 may also induce T lymphocytes to produce both GM-CSF and IL-3, and these two factors would be expected to increase bone marrow hematopoiesis. Erythroid-specific interactions with fibroblastoid cells is suggested by in vitro studies showing binding of erythroid progenitors to a fibroblastoid cell strain and to fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)