Granulocyte/macrophage colony-stimulating factor stimulates monocyte and tissue macrophage proliferation and enhances their responsiveness to macrophage colony-stimulating factor

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a specific humoral growth factor that stimulates both neutrophilic granulocyte and macrophage production by bone marrow hematopoietic progenitor cells. GM-CSF also stimulates the proliferation and clonal growth of both tissue macrophages and blood monocytes. Although at low concentrations GM-CSF was unable to support the long-term growth of tissue macrophages, it greatly enhanced their responsiveness to macrophage CSF (M-CSF, or CSF-1). This effect was also observed by treating macrophages with GM-CSF for a short time. GM-CSF did not compete with M-CSF for binding to M-CSF receptors nor was it inactivated by treatment with anti-M-CSF antiserum. Treatment of tissue macrophages with GM-CSF led to a rapid but transient downregulation of M-CSF receptors; prolonged incubation at 37 degrees C, however, resulted in a restoration and upregulation of M-CSF receptors. Identical effects were observed with both native or recombinant GM-CSF. This study suggests that GM-CSF regulates tissue macrophage production by two modes of action: (a) direct stimulation of macrophage proliferation, and (b) enhancement of their responsiveness to M-CSF.

Proliferation of rat liver macrophages in vitro : Influence of hemopoietic growth factors

“…In this study, we extend these observations by demonstrating that not only L929-CM (M-CSF or CSF-1) but also GM-CSF, which bears no structural similarity to CSF-1, stimulates the proliferation of rat liver macrophages in uitro. These results are comparable to earlier reports on macrophages isolated from other sources: Alveolar macrophages (17, 361, peritoneal exudate macrophages (371, blood monocytes (19) and bone marrow-derived macrophages (19,22) have all been shown to proliferate in uitro on incubation with CSF-1 or GM-CSF. In contrast, IL-2, IL-3 and IL-6, which induce proliferation of macrophages or their precursors in bone marrow and various other organs, did not stimulate liver macrophage proliferation in uitro.…”

Mechanism of Enhanced Hematopoietic Response by Soluble β‐Glucan SCG in Cyclophosphamide‐Treated Mice

“…Like other cytokines, IL-6 has a variety of biological activities, such as induction of B cell differentiation, T cell activation, induction of acute phase proteins, reduction of the G0-residence time of hematopoietic stem cells, and so on (45). GM-CSF is a 23-kd glycoprotein known to be a hematopoietic growth factor required for the proliferation and survival of hematopoietic cells committed to granulocytic and macrophage cell lineages and of myeloid leukemic cells (5,7,24). At least a part of the hematopoietic activity of SCG shown in this study would be explainable by the effects of SCG on the levels of IL-6 and GM-CSF.…”

Examination of survival, proliferation and cell surface antigen expression of human monocytes exposed to macrophage colony‐stimulating factor (M‐CSF)

“…These studies, however, did not investigate the possibility that M-CSF may potentiate the activity of other cytokines to induce proliferation, maturation or activation. Carocciolo et al showed that small doses of GM-CSF in addition to M-CSF produced macrophagic colonies from human bone marrow progenitors [26], and in the murine system, investigators have shown that GM-CSF enhances the responsiveness of macrophages to M-CSF [27], and TNF-a acts synergistically with M-CSF to induce proliferation [28]. Further experiments are needed to determine if M-CSF requires the presence of additional cytokines, such as IL-3, IL-4, YIFN, TNF-a and/or GM-CSF, to induce proliferation or activation of human blood monocytes.…”