Macrophages in haemopoietic and other tissues of the developing mouse detected by the monoclonal antibody F4/80

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 517-526 ◽  
Author(s):  
L. Morris ◽  
C.F. Graham ◽  
S. Gordon
Keyword(s):  
Bone Marrow ◽  
Fetal Liver ◽  
Mononuclear Phagocyte ◽  
Cellular Interactions ◽  
Fetal Tissues ◽  
Prominent Component ◽  
Inflammatory Stimuli ◽  
Monocytes And Macrophages ◽  
Formed Part ◽  
Haemopoietic Cells

Macrophages are widely distributed in lymphohaemopoietic and other tissues of the normal and diseased adult, where they play an important role in host defence and repair. Although the development of haemopoiesis has been well studied in several species, the ontogeny of the mononuclear phagocyte system remains poorly understood. We have used a highly specific mAb, F4/80, to examine the distribution of mature macrophages in the developing mouse, with special reference to their presence in the haemopoietic microenvironment. Monocytes and macrophages were first seen in embryos on day 10 in the yolk sac and liver as well as in mesenchyme. In liver, spleen and bone marrow, there was expansion of this population associated with the initiation of haemopoiesis on days 11, 15 and 17, respectively. Macrophages in these sites formed part of the haemopoietic stroma and their extensively spread plasma membrane processes could be seen making intimate contacts with clusters of differentiating haemopoietic cells. F4/80+ cells were widely dispersed in undifferentiated mesenchymal tissue in organs such as lung, kidney and gut. Numbers of F4/80-labelled cells increased concomitantly with organ growth and local mitoses were evident, as well as actively phagocytic macrophages. Our studies establish that macrophages are among the earliest haemopoietic cells to be produced during development and that they are relatively abundant in fetal tissues in the absence of overt inflammatory stimuli. Their distribution is correlated with the sequential migration of haemopoiesis and they constitute a prominent component of the stroma in fetal liver, spleen red pulp and bone marrow. Apart from a role in haemopoietic cellular interactions, their highly developed endocytic and biosynthetic activities suggest that macrophages contribute major undefined functions during growth, turnover and modelling of fetal tissues.

scholarly journals Mononuclear but Not Polymorphonuclear Phagocyte Depletion Increases Circulation Times and Improves Mammary Tumor-Homing Efficiency of Donor Bone Marrow-Derived Monocytes

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1752
Author(s):  
Francis Combes ◽  
Alexandros Marios Sofias ◽  
Séan Mc Cafferty ◽  
Hanne Huysmans ◽  
Joyca De Temmerman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Cell ◽  
Cellular Level ◽  
Mononuclear Phagocyte ◽  
Circulation Time ◽  
Donor Bone Marrow ◽  
Monocytes And Macrophages ◽  
Macroscopic Findings ◽  
Tumor Accumulation

Tumor associated macrophages are an essential part of the tumor microenvironment. Consequently, bone marrow-derived monocytes (BMDMs) are continuously recruited to tumors and are therefore seen as ideal delivery vehicles with tumor-targeting properties. By using immune cell depleting agents and macroscopic in vivo fluorescence imaging, we demonstrated that removal of endogenous monocytes and macrophages (but not neutrophils) leads to an increased tumor accumulation of exogenously administered BMDMs. By means of intravital microscopy (IVM), we confirmed our macroscopic findings on a cellular level and visualized in real time the migration of the donor BMDMs in the tumors of living animals. Moreover, IVM also revealed that clodronate-mediated depletion drastically increases the circulation time of the exogenously administered BMDMs. In summary, these new insights illustrate that impairment of the mononuclear phagocyte system increases the circulation time and tumor accumulation of donor BMDMs.

Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1357-1372 ◽  
Author(s):  
M.G. Cecchini ◽  
M.G. Dominguez ◽  
S. Mocci ◽  
A. Wetterwald ◽  
R. Felix ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Postnatal Development ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Colony Stimulating Factor ◽  
Monocytes And Macrophages ◽  
Cell Densities ◽  
And Function ◽  
Stimulating Factor

Colony stimulating factor-1 (CSF-1) regulates the survival, proliferation and differentiation of mononuclear phagocytes. The osteopetrotic (op/op) mutant mouse is devoid of CSF-1 due to an inactivating mutation in the CSF-1 gene and is deficient in several mononuclear phagocyte subpopulations. To analyze more fully the requirement for CSF-1 in the establishment and maintenance of mononuclear phagocytes, the postnatal development of cells bearing the macrophage marker antigens F4/80 and MOMA-1, in op/op mice and their normal (+/op or +/+) littermates, were studied during the first three months of life. In normal mice, maximum expression of tissue F4/80+ cells was generally correlated with the period of maximum organogenesis and/or cell turnover. Depending on the tissue, the F4/80+ cell density either decreased, transiently increased or gradually increased with age. In op/op mice, tissues that normally contain F4/80+ cells could be classified into those in which F4/80+ cells were absent and those in which the F4/80+ cell densities were either reduced, normal or initially normal then subsequently reduced. To assess which F4/80+ populations were regulated by circulating CSF-1 in normal mice, op/op mice in which the circulating CSF-1 concentration was restored to above normal levels by daily subcutaneous injection of human recombinant CSF-1 from day 3 were analyzed. These studies suggest that circulating CSF-1 exclusively regulates both the F4/80+ cells in the liver, spleen and kidney and the MOMA-1+ metallophilic macrophages in the spleen. Macrophages of the dermis, bladder, bone marrow and salivary gland, together with a subpopulation in the gut, were partially restored by circulating CSF-1, whereas macrophages of the muscle, tendon, periosteum, synovial membrane, adrenals and the macrophages intimately associated with the epithelia of the digestive tract, were not corrected by restoration of circulating CSF-1, suggesting that they are exclusively locally regulated by this growth factor. Langerhans cells, bone marrow monocytes and macrophages of the thymus and lymph nodes were not significantly affected by circulating CSF-1 nor decreased in op/op mice, consistent with their regulation by other growth factors. These results indicate that important differences exist among mononuclear phagocytes in their dependency on CSF-1 and the way in which CSF-1 is presented to them. They also suggest that the prevalent role of CSF-1 is to influence organogenesis and tissue turnover by stimulating the production of tissue macrophages with local trophic and/or scavenger (physiological) functions. Macrophages involved in inflammatory and immune (pathological) responses appear to be dependent on other factors for their ontogenesis and function.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals A transgenic line that reports CSF1R protein expression provides a definitive marker for the mouse mononuclear phagocyte system

2020 ◽  
Author(s):  
Kathleen Grabert ◽  
Anuj Sehgal ◽  
Katharine M. Irvine ◽  
Evi Wollscheid-Lengeling ◽  
Derya D. Ozdemir ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocyte System ◽  
Lymphoid Tissues ◽  
Direct Role ◽  
Hematopoietic Stem ◽  
C Terminus ◽  
Monocytes And Macrophages ◽  
Macrophage Populations

AbstractThe proliferation, differentiation and survival of cells of the mononuclear phagocyte system (MPS, progenitors, monocytes, macrophages and classical dendritic cells) is controlled by signals from the macrophage colony-stimulating factor receptor (CSF1R). Cells of the MPS lineage have been identified using numerous surface markers and transgenic reporters but none is both universal and lineage-restricted. Here we report the development and characterization of a novel CSF1R reporter mouse. A Fusion Red (FRed) cassette was inserted in-frame with the C-terminus of CSF1R, separated by a T2A-cleavable linker. The insertion had no effect of CSF1R expression or function. CSF1R-FRed was expressed in monocytes and macrophages and absent from granulocytes and lymphocytes. In bone marrow, CSF1R-FRed was absent in lineage-negative hematopoietic stem cells (HSC), arguing against a direct role for CSF1R in myeloid lineage commitment. It was highly-expressed in marrow monocytes and common myeloid progenitors (CMP) but significantly lower in granulocyte-macrophage progenitors (GMP). In sections of bone marrow, CSF1R-FRed was also detected in osteoclasts, CD169+ resident macrophages and, consistent with previous mRNA analysis, in megakaryocytes. In lymphoid tissues, CSF1R-FRed highlighted diverse MPS populations including classical dendritic cells. Whole mount imaging of non-lymphoid tissues in mice with combined CSF1R-FRed/Csf1r-EGFP confirmed the restriction of CSF1R expression to MPS cells. The two markers highlight the remarkable abundance and regular distribution of tissue MPS cells including novel macrophage populations within tendon and skeletal muscle and underlying the mesothelial/serosal/capsular surfaces of every major organ. The CSF1R-FRed mouse provides a novel reporter with exquisite specificity for cells of the MPS.

scholarly journals Human fetal liver MSCs are more effective than adult bone marrow MSCs for their immunosuppressive, immunomodulatory, and Foxp3+ T reg induction capacity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi Yu ◽  
Alejandra Vargas Valderrama ◽  
Zhongchao Han ◽  
Georges Uzan ◽  
Sina Naserian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Fetal Liver ◽  
Cytotoxic T Cells ◽  
Cell Contact ◽  
Adult Bone Marrow ◽  
Adult Bone

Abstract Background Mesenchymal stem cells (MSCs) exhibit active abilities to suppress or modulate deleterious immune responses by various molecular mechanisms. These cells are the subject of major translational efforts as cellular therapies for immune-related diseases and transplantations. Plenty of preclinical studies and clinical trials employing MSCs have shown promising safety and efficacy outcomes and also shed light on the modifications in the frequency and function of regulatory T cells (T regs). Nevertheless, the mechanisms underlying these observations are not well known. Direct cell contact, soluble factor production, and turning antigen-presenting cells into tolerogenic phenotypes, have been proposed to be among possible mechanisms by which MSCs produce an immunomodulatory environment for T reg expansion and activity. We and others demonstrated that adult bone marrow (BM)-MSCs suppress adaptive immune responses directly by inhibiting the proliferation of CD4+ helper and CD8+ cytotoxic T cells but also indirectly through the induction of T regs. In parallel, we demonstrated that fetal liver (FL)-MSCs demonstrates much longer-lasting immunomodulatory properties compared to BM-MSCs, by inhibiting directly the proliferation and activation of CD4+ and CD8+ T cells. Therefore, we investigated if FL-MSCs exert their strong immunosuppressive effect also indirectly through induction of T regs. Methods MSCs were obtained from FL and adult BM and characterized according to their surface antigen expression, their multilineage differentiation, and their proliferation potential. Using different in vitro combinations, we performed co-cultures of FL- or BM-MSCs and murine CD3+CD25−T cells to investigate immunosuppressive effects of MSCs on T cells and to quantify their capacity to induce functional T regs. Results We demonstrated that although both types of MSC display similar cell surface phenotypic profile and differentiation capacity, FL-MSCs have significantly higher proliferative capacity and ability to suppress both CD4+ and CD8+ murine T cell proliferation and to modulate them towards less active phenotypes than adult BM-MSCs. Moreover, their substantial suppressive effect was associated with an outstanding increase of functional CD4+CD25+Foxp3+ T regs compared to BM-MSCs. Conclusions These results highlight the immunosuppressive activity of FL-MSCs on T cells and show for the first time that one of the main immunoregulatory mechanisms of FL-MSCs passes through active and functional T reg induction.

T Cell Progenitors in the Murine Fetal Liver: Differences from Those in the Adult Bone Marrow

1997 ◽  
Vol 177 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Yoshihiro Watanabe ◽  
Yuichi Aiba ◽  
Yoshimoto Katsura
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Fetal Liver ◽  
Adult Bone Marrow ◽  
T Cell Progenitors ◽  
Adult Bone

scholarly journals The Mononuclear Phagocyte System: The Relationship between Monocytes and Macrophages

2019 ◽  
Vol 40 (2) ◽  
pp. 98-112 ◽  
Author(s):  
David A. Hume ◽  
Katharine M. Irvine ◽  
Clare Pridans
Keyword(s):  
Mononuclear Phagocyte ◽  
Mononuclear Phagocyte System ◽  
Monocytes And Macrophages ◽  
The Relationship

scholarly journals CD44 Regulates Hematopoietic Progenitor Distribution, Granuloma Formation, and Tumorigenicity

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2217-2233 ◽  
Author(s):  
Rudolf Schmits ◽  
Jorge Filmus ◽  
Nicole Gerwin ◽  
Giorgio Senaldi ◽  
Friedemann Kiefer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Growth ◽  
Fetal Liver ◽  
Cell Types ◽  
Neurological Deficits ◽  
Compensatory Response ◽  
Colony Forming Unit ◽  
Numerous Cell ◽  
Tumor Studies ◽  
Inhibition Of Tumor Growth

CD44 is expressed in various isoforms on numerous cell types and tissues during embryogenesis and in the mature organism. CD44 may also be involved in tumor growth. To study the multiple roles of CD44, we abolished expression of all known isoforms of CD44 in mice by targeting exons encoding the invariant N-terminus region of the molecule. Surprisingly, mice were born in Mendelian ratio without any obvious developmental or neurological deficits. Hematological impairment was evidenced by altered tissue distribution of myeloid progenitors with increased levels of colony-forming unit–granulocyte-macrophage (CFU-GM) in bone marrow and reduced numbers of CFU-GM in spleen. Fetal liver colony-forming unit–spleen and granulocyte colony-stimulating factor mobilization assays, together with reduced CFU-GM in peripheral blood, suggested that progenitor egress from bone marrow was defective. In what was either a compensatory response to CD44 deficiency or an immunoregulatory defect, mice also developed exaggerated granuloma responses to Cryotosporidium parvum infection. Finally, tumor studies showed that SV40-transformed CD44-deficient fibroblasts were highly tumorigenic in nude mice, whereas reintroduction of CD44s expression into these fibroblasts resulted in a dramatic inhibition of tumor growth.

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