Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

Guilliams, Martin; Kleer, Ismé de; Henri, Sandrine; Post, S.; Vanhoutte, Leen; Prijck, Sofie De; Deswarte, Kim; Malissen, Bernard; Hammad, Hamida; Lambrecht, Bart N.

doi:10.1084/jem.20131199

Cited by 1,017 publications

(1,207 citation statements)

References 59 publications

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“…The lack of effect on other M1/M2 markers is perhaps a reflection of the lack of well-defined markers to unambiguously define the human macrophage activation state (47). It could also be explained by the different methods used for achieving monocyte differentiation and macrophage stimulation; in our studies, we used GM-CSF as a differentiation factor to model AMs (48,49). GM-CSF also promotes an M1-like phenotype, more closely mimicking activated AMs that would be present in the alveoli of patients with ARDS.…”

Section: Msc-derived Ev-treated Murine Amsmentioning

confidence: 90%

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Morrison

Jackson

Cunningham

et al. 2017

Am J Respir Crit Care Med

573

490

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Rationale: Acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure in critically ill patients. Mesenchymal stromal cells (MSCs) are a promising candidate for a cell-based therapy. However, the mechanisms of MSCs' effects in ARDS are not well understood. In this study, we focused on the paracrine effect of MSCs on macrophage polarization and the role of extracellular vesicle (EV)-mediated mitochondrial transfer.Objectives: To determine the effects of human MSCs on macrophage function in the ARDS environment and to elucidate the mechanisms of these effects.Methods: Human monocyte-derived macrophages (MDMs) were studied in noncontact coculture with human MSCs when stimulated with LPS or bronchoalveolar lavage fluid (BALF) from patients with ARDS. Murine alveolar macrophages (AMs) were cultured ex vivo with/without human MSC-derived EVs before adoptive transfer to LPS-injured mice.Measurements and Main Results: MSCs suppressed cytokine production, increased M2 macrophage marker expression, and augmented phagocytic capacity of human MDMs stimulated with LPS or ARDS BALF. These effects were partially mediated by CD44-expressing EVs. Adoptive transfer of AMs pretreated with MSCderived EVs reduced inflammation and lung injury in LPS-injured mice. Inhibition of oxidative phosphorylation in MDMs prevented the modulatory effects of MSCs. Generating dysfunctional mitochondria in MSCs using rhodamine 6G pretreatment also abrogated these effects.Conclusions: In the ARDS environment, MSCs promote an antiinflammatory and highly phagocytic macrophage phenotype through EV-mediated mitochondrial transfer. MSC-induced changes in macrophage phenotype critically depend on enhancement of macrophage oxidative phosphorylation. AMs treated with MSCderived EVs ameliorate lung injury in vivo.

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Section: Msc-derived Ev-treated Murine Amsmentioning

confidence: 90%

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Morrison

Jackson

Cunningham

et al. 2017

Am J Respir Crit Care Med

573

490

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“…This alveolar phase of lung growth lasts until 3 years of age and is controlled by many growth factors and cytokines that could also influence (Schittny et al, 2008). Fetal lung is first populated around E12 by CD45 + yolk sac-derived macrophages (De Kleer et al, 2014;Guilliams et al, 2013;Schulz et al, 2012;van de Laar et al, 2016). We recently have shown that this first wave of yolk sac-derived macrophages is followed by a consecutive wave of fetal liver-derived monocytes that enter the lung around E18, the start of the saccular phase in mice, and give rise to alveolar macrophages (AM) under the influence of GM-CSF van de Laar et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung

et al. 2016

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“…A unified nomenclature has recently been proposed to attempt to circumvent this fundamental problem in which MPS cells can be classified primarily by their ontogeny and secondarily by their location, function, and phenotype in the steady-state and in inflammatory conditions (13). Even though a number of articles using sophisticated in vivo technology in mice have recently appeared addressing the origins of tissue macrophages during development, there is still debate around the fundamental question of the contribution, if any, of blood monocytes, including their subpopulations, to tissue macrophages in the adult at steady-state, and also to what extent local macrophage proliferation contributes to their homeostatic control or to that during inflammatory reactions (3,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

Specific Contributions of CSF-1 and GM-CSF to the Dynamics of the Mononuclear Phagocyte System

Louis

Cook

Lacey

et al. 2015

The Journal of Immunology

109

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M-CSF (or CSF-1) and GM-CSF can regulate the development and function of the mononuclear phagocyte system (MPS). To address some of the outstanding and sometimes conflicting issues surrounding this biology, we undertook a comparative analysis of the effects of neutralizing mAbs to these CSFs on murine MPS populations in the steady-state and during acute inflammatory reactions. CSF-1 neutralization, but not of GM-CSF, in normal mice rapidly reduced the numbers of more mature Ly6C− monocytes in blood and bone marrow, without any effect on proliferating precursors, and also the numbers of the resident peritoneal macrophages, observations consistent with CSF-1 signaling being essential only at a relatively late state in steady-state MPS development; in contrast, GM-CSF neutralization had no effect on the numbers of these particular populations. In Ag-induced peritonitis (AIP), thioglycolate-induced peritonitis, and LPS-induced lung inflammation, CSF-1 neutralization lowered inflammatory macrophage number; in the AIP model, this reduced number was not due to suppressed proliferation. More detailed studies with the convenient AIP model indicated that CSF-1 neutralization led to a relatively uniform reduction in all inflammatory cell populations; GM-CSF neutralization, in contrast, was more selective, resulting in the preferential loss among the MPS populations of a cycling, monocyte-derived inflammatory dendritic cell population. Some mechanistic options for the specific CSF-dependent biologies enumerated are discussed.

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Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

Abstract: Alveolar macrophages differentiate from fetal monocytes in a GM-CSF–dependent fashion and colonize the alveolar space within a few days after birth.

Cited by 1,017 publications

References 59 publications

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung

Specific Contributions of CSF-1 and GM-CSF to the Dynamics of the Mononuclear Phagocyte System

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