Interleukin-6 synergizes with M-CSF in the formation of macrophage colonies from purified human marrow progenitor cells

Bot, Fredrik J.; Eijk, L van; Broeders, L; La, Aarden; Löwenberg, Bob

doi:10.1182/blood.v73.2.435.435

Cited by 84 publications

(12 citation statements)

References 14 publications

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“…The results obtained from serum-containing and serum-free culture experiments show that the humoral factor(s) in serum drives CD14 1 monocytes into CD14 1 CD1a 2 macrophages but not into CD14 2 CD1a 1 DCs in the presence of GM-CSF plus IL-4, thus leading to the assumption that the factor(s) in the serum acts on CD14 1 monocytes to modify their differentiation. Because IL-6 was reported to have the potential to promote monocyte±macrophage colony formation by haemopoietic progenitor cells (Bot et al, 1989;Jansen et al, 1992), we considered that IL-6 may be involved in the shift of CD14 1 monocytes to CD14 1 CD1a 2 macrophages in cultures supported by GM-CSF plus IL-4. Accordingly, we first examined whether blocking of the signals induced by IL-6 would affect differentiation of CD14 1 monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Role of IL-6-mediated signals in the differentiation of CD14 1 cells The data shown in Fig 1C and D suggest that serum components, including cytokines, may influence the differentiation of CD14 1 monocytes into macrophages. Previous reports demonstrated that IL-6 supports the development of monocytes±macrophages (Bot et al, 1989;Jansen et al, 1992). It is possible that IL-6 in the serum may be responsible for the population of CD14 1 CD1a 2 cells in serum-containing cultures supplemented with GM-CSF plus IL-4.…”

Section: Phenotype Of Cells In Culture Of Cd14 1 Cells In the Presencmentioning

confidence: 98%

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Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells

et al. 2000

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Summary. Peripheral blood monocytes are common precursor cells of dendritic cells (DCs) and macrophages. We have searched for factors with the potential to regulate the differentiation of monocytes to DCs and macrophages. When CD141 monocytes are cultured with granulocyte± macrophage colony-stimulating factor (GM-CSF) and interleukin (IL) 4, the CD14 1 CD1a 2 population, which consists of macrophages, was found in the serum-containing cultures but not in the serum-free cultures. Addition of IL-6 receptor-neutralizing monoclonal antibody (mAb) or gp130-neutralizing mAb to the serum-containing cultures resulted in a decreased population of CD141 CD1a 2 cells. An increase in the CD141 CD1a 2 population with reduction in CD14 2 CD1a 1 DCs was observed with the addition of IL-6 to cultures, whereas IL-11, leukaemia inhibitory factor, oncostatin M or macrophage colony-stimulating factor did not affect the differentiation of monocytes in the presence of GM-CSF plus IL-4. This effect of IL-6 was blocked by tumour necrosis factor a (TNF-a), lipopolysaccharide (LPS), IL-1b, CD40 ligand (CD40L) and transforming growth factor b1 (TGF-b1). Among these factors, TNF-a was most potent in interfering with the action of IL-6. These results suggest that IL-6 inhibits the differentiation of monocytes to DCs by promoting their differentiation toward macrophages, which is modulated by factors such as TNF-a, LPS, IL-1b, CD40L and TGF-b1.

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Section: Discussionmentioning

confidence: 99%

Section: Phenotype Of Cells In Culture Of Cd14 1 Cells In the Presencmentioning

confidence: 98%

Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells

et al. 2000

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“…'~~,~~~ Recently interleukin-6 was demonstrated to interact synergistically with GM-CSF to enhance he-matop~iesis,'~~ however another study failed to support these observations. 143 The myelopoiesis enhancing activity attributed to IL-6 resembles that of G-CSF, with which IL-6 has 25.7% amino acid suggesting a role for IL-6 in the treatment of various granulocytopenias.…”

Section: Interleukin-6mentioning

confidence: 99%

Interleukins: Biological Properties and Therapeutic Potential

Elmslie

Dow

Ogilvie³

1991

Veterinary Internal Medicne

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EFFECTIVE IMMUNE responses are dependent, in part, on interactions between macrophages, T lymphocytes, and B lymphocytes. T lymphocytes are essential for coordination and stimulation of various components of the immune system. Once activated by a complex of antigen plus major histocompatibility complex (MHC) and appropriate costimulatory signals, T lymphocytes release a variety of biologically active substances collectively referred to as lymphokines. The term cytukine refers to biologically active cell products and includes both monokines (macrophage-derived) and lymphokines.Lymphokines are glycoproteins that may exert their effect locally, on the cells from which they were secreted (autocrine effect), or on neighboring cells (paracrine effect). Lymphokines also acquire access to the general circulation and exert systemic effects (endocrine effect).' Unlike antibodies, the tridimensional structure of lymphokines is independent of the stimulating antigen.The term interleukin was adopted to describe those lymphokines and monokines that act on leukocytes.2 This classification scheme has become increasingly arbitrary since it is apparent that interleukins exert multiple effects on cells other than leukocytes and that there are

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“…The mononuclear phagocyte (MNP) lineage depends critically on the presence of the monocyte-macrophage colony-stimulating factor (CSF-1 or M-CSF) but their differentiation may be modulated by the presence of other growth factors, such as interleukin (IL) -6 and the granulocyte-macrophage colony-stimulating factor (GM-CSF) [1]. For example, IL-6 has been reported to synergize with CSF-1 [2] and GM-CSF [3] in the formation of M colonies from human bone marrow progenitor cells and to promote maturation of monocytes into M [4]. GM-CSF is known to stimulate monocyte and tissue M proliferation [5] and to enhance CSF-1-induced proliferation of M [5].…”

Section: Introductionmentioning

confidence: 99%

CSF-1 regulation of I6 gene expression by murine macrophages: a pivotal role for GM-CSF

Evans

Shultz

Dranoff

et al. 1998

Journal of Leukocyte Biology

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We test the hypothesis that the monocyte-macrophage colony-stimulating factor (CSF-1 or M-CSF) plays a major role in the inflammatory responses of M by acting as a priming agent that heightens their responsiveness to secondary stimulation by other mediators. We previously reported that CSF-1 induced peritoneal M (PM ) to transcribe several genes including interleukin-6 (Il6) and granulocyte-macrophage colony-stimulating factor (Csfgm). It was reported that the Il6 and Csfgm genes were individually regulated by different pathways but it was not clear to what extent the two genes interacted during M -mediated inflammatory responses. We now show that CSF-1 induces the release of bioactive GM-CSF from mouse resident PM . GM-CSF induces Il6 gene expression and synergizes with CSF-1 to induce the release of large amounts of IL-6. PM from C57BL/6J-Csfgm null mice were shown to release minimal IL-6 in response to CSF-1 and to express a much reduced response to the highly stimulatory combination of CSF-1 and lipopolysaccharide (LPS). Exogenous recombinant GM-CSF restored the IL-6 response of GM-CSF null PM to a great extent but not completely. As controls, three other recombinant proteins were tested but of these only tumor necrosis factor ␣ (TNF-␣) was shown to synergize with both CSF-1 and GM-CSF. Using PM from mice deficient in the expression of the Il6 gene, it was shown that they released two-to threefold more GM-CSF in response to CSF-1 than their control counterparts. However, an exogenous supply of recombinant IL-6 had no effect on GM-CSF release. The data indicate that the pathways regulating Il6 gene expression are under the control of a complex network of cytokine interactions involving at least CSF-1, GM-CSF, and TNF-␣, with the added possibility that IL-6 may exert modulatory activity within this network. J. Leukoc. Biol. 64: 810-816; 1998.

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Interleukin-6 synergizes with M-CSF in the formation of macrophage colonies from purified human marrow progenitor cells

Cited by 84 publications

References 14 publications

Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells

Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells

Interleukins: Biological Properties and Therapeutic Potential

CSF-1 regulation of I6 gene expression by murine macrophages: a pivotal role for GM-CSF

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