Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effects of GM-CSF on polymorphonuclear leukocytes (PMN) more extensively. Using Northern blot analysis, we show that PMN are able to accumulate mRNAs for different cytokines, including tumor necrosis factor-a (TNF-a); G-CSF, and M-CSF, all of which are involved in inflammation and hematopoiesis. Biological assays and immunoassays demonstrate that PMN translate these mRNAs, except TNF-a, into secretory proteins. However, the expression of these cytokines is dependent on stimulation by exogenous signals, preferentially provided by the T cell-derived lymphokine GM-CSF.

MCP-1 is selectively expressed in the late phase by cytokine-stimulated human neutrophils: TNF-α plays a role in maximal MCP-1 mRNA expression

“…Among other PMN-stimulating cytokines, GM-CSF prolongs PMN survival by inhibiting programmed cell death [42,43] and also stimulates PMN to express several cytokine mRNAs [5,11,16,20,21]. Although rGM-CSF was able to induce a low-level MCP-1 mRNA accumulation in PMN, addition of neutralizing anti-GM-CSF IgG had no effect on the expression of MCP-1 mRNA.…”

“…It is now well known that many cytokines can be produced by stimulated human PMN [5]. These include IL-1␣ and ␤ [6], tumor necrosis factor ␣ (TNF-␣) [7], IL-1 receptor antagonist (IL-1Ra) [8,9], transforming growth factor ␤ (TGF-␤) [10], IL-6 [11,12], IL-8 [13][14][15][16], interferon-␥ (IFN-␥) [17], macrophage inflammatory protein-1␣ (MIP-1␣) and MIP-1␤ [18], IFN-␥-inducible protein-10 (IP-10) [19], granulocyte-macrophage colony-stimulating factor (GM-CSF) [20], granulocyte-CSF (G-CSF) [21], and macrophage-CSF (M-CSF) [21].…”

Inflammation and skeletal metastasis

“…67 A feedback loop has been suggested, which links the macrophage production of cytokines IL-1 and TNF with the induction of colony-stimulating factors (M-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF)) in the surrounding cells of the inflammatory microenvironment such as T cells, endothelial cells, fibroblasts and epithelial cells. [68][69][70][71][72][73] The CSFs can further promote the proliferation/survival or activation of macrophages and neutrophils to enhance the production of factors that sustain a chronic inflammatory stage. The analysis of Lewis lung carcinoma (LLC) cell-secreted factors further revealed the complex interactions in the tumor milieu.…”

Cross-Linking of Human FcγRIIIb Induces the Production of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor by Polymorphonuclear Neutrophils

“…Comparable results have been reported by Matute-Bello et al (61) in bronchoalveolar lavage fluid from patients with the acute respiratory distress syndrome. It is known that GM-CSF can induce the secretion of G-CSF by PMNs (62). It would thus be interesting to study the kinetics of GM-CSF and G-CSF production in the CD16-stimulated PMN model, to address the issue as to whether the G-CSF expression results from that of GM-CSF.…”