Two distinct cell populations are obtained from human blood monocytes cultured with M-CSF, GM-CSF and IL-4

Baron, Carole; Scholl, Susy; Bausinger, Huguette; Hanau, Daniel; Pouillart, P; Goud, Bruno; Salamero, Jean

doi:10.1016/s0959-8049(99)00091-x

Cited by 7 publications

(5 citation statements)

References 4 publications

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“…In fact, these changes may be due to CSN1S1 or be mediated by the induction of GM-CSF expression and subsequent autocrine stimulation of monocytic cells. The latter is suggested by the observation that human blood monocytes differentiate into dendritic or macrophage-like cell types when stimulated with GM-CSF (33,44,45). Furthermore, direct stimulation of monocytes with GM-CSF induced upregulation of the otherwise constitutively expressed CSF2RA (46).…”

Section: Discussionmentioning

confidence: 98%

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Vordenbäumen

Braukmann

Petermann

et al. 2011

The Journal of Immunology

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Caseins are major constituents of mammalian milks that are thought to be exclusively expressed in mammary glands and to function primarily as a protein source, as well as to ameliorate intestinal calcium uptake. In addition, proinflammatory and immunomodulatory properties have been reported for bovine caseins. Our aim was to investigate whether human casein α s1 (CSN1S1) is expressed outside the mammary gland and possesses immunomodulatory functions in humans as well. For this purpose, CSN1S1 mRNA was detected in primary human monocytes and CD4+ and CD8+ T cells, but not in CD19+ B cells. CSN1S1 protein was traceable in supernatants of cultured primary human CD14+ monocytes by ELISA. Similarly, CSN1S1 mRNA and protein were detected in the human monocytic cell lines HL60, U937, and THP1 but not in Mono Mac 6 cells. Moreover, permeabilized human monocytes and HL60 cells could be stained by immunofluorescence, indicating intracellular expression. Recombinant human CSN1S1 was bound to the surface of Mono Mac 6 cells and upregulated the expression of GM-CSF mRNA in primary human monocytes and Mono Mac 6 cells in a time- and concentration-dependent manner. A similar increase in GM-CSF protein was found in the culture supernatants. CSN1S1-dependent upregulation of GM-CSF was specifically blocked by the addition of the p38 MAPK inhibitor ML3403. Our results indicated that human CSN1S1 may possess an immunomodulatory role beyond its nutritional function in milk. It is expressed in human monocytes and stimulates the expression of the proinflammatory cytokine GM-CSF.

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Section: Discussionmentioning

confidence: 98%

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Vordenbäumen

Braukmann

Petermann

et al. 2011

The Journal of Immunology

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“…M-CSF is an important cytokine for macrophage differentiation [46,47], survival [48], and activation [49,50]. M-CSF is also a product of macrophage alternative activation [19].…”

Section: Discussionmentioning

confidence: 99%

Elevated gelatinase activity in pulmonary alveolar proteinosis: role of macrophage-colony stimulating factor

Bonfield

Swaisgood

Barna

et al. 2005

Journal of Leukocyte Biology

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Pulmonary alveolar proteinosis (PAP) is an anti-granulocyte macrophage-colony stimulating factor (GM-CSF) autoimmune disease resulting in the accumulation of phospholipids in the alveoli. GM-CSF knockout (KO) mice exhibit a strikingly similar lung pathology to patients with PAP. The lack of functionally active GM-CSF correlates with highly elevated concentrations of M-CSF in the lungs of PAP patients and GM-CSF KO mice. M-CSF has been associated with alternative macrophage activation, and in models of pulmonary fibrosis, M-CSF also contributes to tissue resorption and fibrosis. Matrix metalloproteinase-2 (MMP-2) and MMP-9 have been implicated in extracellular matrix degradation in animal models of fibrosis and asthma. We show for the first time that the lungs of PAP patients contain highly elevated levels of MMP-2 and MMP-9. PAP broncholaveolar lavage (BAL) cells but not bronchial epithelial cells expressed increased MMP-2 and MMP-9 mRNA relative to healthy controls. Both MMPs were detectable as pro and active proteins by gelatin zymography; and by fluorometric global assay, PAP-MMP activity was elevated. BAL cells/fluids from GM-CSF KO mice also demonstrated significantly elevated MMP-2 and MMP-9 gene expression, protein, and activity. Finally, PAP patients undergoing GM-CSF therapy exhibited significantly reduced MMPs and M-CSF. These data suggest that in the absence of GM-CSF, excess M-CSF in PAP may redirect alveolar macrophage activation, thus potentially contributing to elevated MMP expression in the lung.

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“…It has been suggested that the presence of colony stimulating factor-1 (CSF-1), a macrophage-specific growth factor which is abundant in many tumours, will lead to TAM and may divert effective maturation from DCs, which are potent APCs, thereby perturbing efficient immune stimulation. 12,13 However, in some instances there are signs of an effective immune response occurring at the tumour site. Thus, the presence of specialised CD4+ T cells in the TME, when found to localise to the germinal centres of peri-tumoural tertiary lymphoid structures in extensively infiltrated neoplastic lesions, predicted improved outcome in breast carcinoma patients.…”

Section: The Reality Of Immune Therapy In Clinical Practicementioning

confidence: 99%

“…We have previously shown that it modifies DC differentiation prior to the terminal differentiation step by tumour necrosis factor, while fully mature DCs will not be modified by CSF1. 13 • Finally, we can use the notion of checkpoint modification as analogous to the balance of the centre of gravity of the immune response.…”

Section: Modulations -Adaptations To the Individual Immune Response S...mentioning

confidence: 99%

Fundamental Principles of Raising an Antitumour Immune Response in Vivo: A Complex Model, a Case Report, and a Perspective

Scholl

2014

EMJ Oncol

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In preclinical model systems, the fundamental principles underlying a successful and durable anti-tumour immune response are well demonstrated. In clinical practice, significant successes in Phase III trials have been few over the last decades, but the field has gained tremendous interest following recent advances showing the activity of checkpoint blockade inhibitors. Still, at this time we do not fully understand why some people respond while others do not; nor do we completely understand which clinical and immunological monitoring tools we need to put in place to make immunotherapy a more controlled medical science. Reviewing recent evidence suggests that for a successful and controlled immunotherapy, we may need to juggle with several conditions at the same time; there is a need for the endogenous or exogenous addition of tumour antigens for a favourable tumour microenvironment, and for an immune system which remains actionable towards T cell (effector) activity by checkpoint blockade inhibitors.

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Two distinct cell populations are obtained from human blood monocytes cultured with M-CSF, GM-CSF and IL-4

Cited by 7 publications

References 4 publications

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Elevated gelatinase activity in pulmonary alveolar proteinosis: role of macrophage-colony stimulating factor

Fundamental Principles of Raising an Antitumour Immune Response in Vivo: A Complex Model, a Case Report, and a Perspective

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