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In vitro induction of inhibitory macrophage differentiation by granulocyte-macrophage colony-stimulating factor, stem cell factor and interferon-gamma from lineage phenotypes-negative c-kit-positive murine hematopoietic progenitor cells.
Immunol Lett. 2004 Feb 15; 91(2-3):221-7.IL

Abstract

CD11b+Gr-1+ inhibitory macrophages (iMacs) were implicated in profound depression of T cell functions sometimes observed during cyclophosphamide treatments and overwhelming infections, through a secretion of nitric oxide (NO). Myeloid origin and maturation stages of iMacs are still unknown. As tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) contributed crucially to the activation of inducible NO synthase (iNOS) gene transcription and to the differentiation of macrophages, we tested their roles in the induction of iMacs differentiation from bone marrow hematopoietic progenitor cells (HPC) of uncompromised mice. Lineage phenotypes-negative (lin)) c-kit+ cells of Balb/c mice were cultured 6 days with granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF, c-kit ligand) in presence or not of TNF-alpha or IFN-gamma. CD11b+Gr-1+ cells only derived in presence of [GM-CSF + SCF + TNF-alpha] or [GM-CSF + SCF + IFN-gamma] could express iNOS upon in vitro stimulation with [IFN-gamma + TNF-alpha] or [IFN-gamma + LPS] known to boost iNOS expression in murine macrophages. However, whereas [GM-CSF + SCF + TNF-alpha] induced only weakly iMacs generation and contributed also to the differentiation of CD11b+Gr-1-CD11c+ myeloid dendritic cells, [GM-CSF + SCF + IFN-gamma] induced exclusively and importantly iMacs differentiation. Moreover [GM-CSF + SCF + IFN-gamma]-generated iMacs were more mature than [GM-CSF + SCF + TNF-alpha]-derived iMacs since IFN-gamma increased more strongly CD11b+Gr-1+ cells expressing Ly-6C and generated lesser cells expressing MHC class II and CD86 molecules. Finally [GM-CSF + SCF + IFN-gamma]-generated CD11b+ cells showing a powerful suppressive activity on T cell proliferations, correlated with NO secretion. In conclusion, our study showed, for the first time, that IFN-gamma induced very efficiently the differentiation of functional iMacs from lin- c-kit+ murine HPC in vitro, and indicated clearly that iMacs progenitors may be present in bone marrow of naïve mice.

Authors+Show Affiliations

Immuno-endocrinology Unit, ENVN/INRA/University, ENVN, Atlanpole-La Chantrerie, BP 40706, 44307 Nantes Cedex 03, France.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15019293

Citation

Ferret-Bernard, Stéphanie, et al. "In Vitro Induction of Inhibitory Macrophage Differentiation By Granulocyte-macrophage Colony-stimulating Factor, Stem Cell Factor and Interferon-gamma From Lineage Phenotypes-negative C-kit-positive Murine Hematopoietic Progenitor Cells." Immunology Letters, vol. 91, no. 2-3, 2004, pp. 221-7.
Ferret-Bernard S, Saï P, Bach JM. In vitro induction of inhibitory macrophage differentiation by granulocyte-macrophage colony-stimulating factor, stem cell factor and interferon-gamma from lineage phenotypes-negative c-kit-positive murine hematopoietic progenitor cells. Immunol Lett. 2004;91(2-3):221-7.
Ferret-Bernard, S., Saï, P., & Bach, J. M. (2004). In vitro induction of inhibitory macrophage differentiation by granulocyte-macrophage colony-stimulating factor, stem cell factor and interferon-gamma from lineage phenotypes-negative c-kit-positive murine hematopoietic progenitor cells. Immunology Letters, 91(2-3), 221-7.
Ferret-Bernard S, Saï P, Bach JM. In Vitro Induction of Inhibitory Macrophage Differentiation By Granulocyte-macrophage Colony-stimulating Factor, Stem Cell Factor and Interferon-gamma From Lineage Phenotypes-negative C-kit-positive Murine Hematopoietic Progenitor Cells. Immunol Lett. 2004 Feb 15;91(2-3):221-7. PubMed PMID: 15019293.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro induction of inhibitory macrophage differentiation by granulocyte-macrophage colony-stimulating factor, stem cell factor and interferon-gamma from lineage phenotypes-negative c-kit-positive murine hematopoietic progenitor cells. AU - Ferret-Bernard,Stéphanie, AU - Saï,Pierre, AU - Bach,Jean-Marie, PY - 2003/09/22/received PY - 2003/12/05/revised PY - 2003/12/18/accepted PY - 2004/3/17/pubmed PY - 2004/10/28/medline PY - 2004/3/17/entrez SP - 221 EP - 7 JF - Immunology letters JO - Immunol Lett VL - 91 IS - 2-3 N2 - CD11b+Gr-1+ inhibitory macrophages (iMacs) were implicated in profound depression of T cell functions sometimes observed during cyclophosphamide treatments and overwhelming infections, through a secretion of nitric oxide (NO). Myeloid origin and maturation stages of iMacs are still unknown. As tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) contributed crucially to the activation of inducible NO synthase (iNOS) gene transcription and to the differentiation of macrophages, we tested their roles in the induction of iMacs differentiation from bone marrow hematopoietic progenitor cells (HPC) of uncompromised mice. Lineage phenotypes-negative (lin)) c-kit+ cells of Balb/c mice were cultured 6 days with granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF, c-kit ligand) in presence or not of TNF-alpha or IFN-gamma. CD11b+Gr-1+ cells only derived in presence of [GM-CSF + SCF + TNF-alpha] or [GM-CSF + SCF + IFN-gamma] could express iNOS upon in vitro stimulation with [IFN-gamma + TNF-alpha] or [IFN-gamma + LPS] known to boost iNOS expression in murine macrophages. However, whereas [GM-CSF + SCF + TNF-alpha] induced only weakly iMacs generation and contributed also to the differentiation of CD11b+Gr-1-CD11c+ myeloid dendritic cells, [GM-CSF + SCF + IFN-gamma] induced exclusively and importantly iMacs differentiation. Moreover [GM-CSF + SCF + IFN-gamma]-generated iMacs were more mature than [GM-CSF + SCF + TNF-alpha]-derived iMacs since IFN-gamma increased more strongly CD11b+Gr-1+ cells expressing Ly-6C and generated lesser cells expressing MHC class II and CD86 molecules. Finally [GM-CSF + SCF + IFN-gamma]-generated CD11b+ cells showing a powerful suppressive activity on T cell proliferations, correlated with NO secretion. In conclusion, our study showed, for the first time, that IFN-gamma induced very efficiently the differentiation of functional iMacs from lin- c-kit+ murine HPC in vitro, and indicated clearly that iMacs progenitors may be present in bone marrow of naïve mice. SN - 0165-2478 UR - https://www.unboundmedicine.com/medline/citation/15019293/In_vitro_induction_of_inhibitory_macrophage_differentiation_by_granulocyte_macrophage_colony_stimulating_factor_stem_cell_factor_and_interferon_gamma_from_lineage_phenotypes_negative_c_kit_positive_murine_hematopoietic_progenitor_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165247803003225 DB - PRIME DP - Unbound Medicine ER -