scholarly journals miR-223 suppresses differentiation of tumor-induced CD11b+Gr1+myeloid-derived suppressor cells from bone marrow cells

2011 ◽  
Vol 129 (11) ◽  
pp. 2662-2673 ◽  
Author(s):  
Qiaofei Liu ◽  
Miaomiao Zhang ◽  
Xingran Jiang ◽  
Zhiqian Zhang ◽  
Lingyun Dai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Marrow Cells

scholarly journals In Vitro 3D Staphylococcus aureus Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1446
Author(s):  
Marloes I. Hofstee ◽  
Anja Heider ◽  
Sonja Häckel ◽  
Caroline Constant ◽  
Martijn Riool ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Marrow ◽  
T Cell ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Numbers ◽  
Biomarker Analysis ◽  
Marrow Cells

Staphylococcus aureus is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic S. aureus infections, it remains unknown whether SACs directly trigger MDSC expansion. To investigate this, a previously developed 3D in vitro SAC model was co-cultured with murine and human bone marrow cells. Subsequently, it was shown that SAC-exposed human CD11blow/− myeloid cells or SAC-exposed murine CD11b+ Gr-1+ cells were immunosuppressive mainly by reducing absolute CD4+ and CD8α+ T cell numbers, as shown in T cell proliferation assays and with flow cytometry. Monocytic MDSCs from mice with an S. aureus bone infection also strongly reduced CD4+ and CD8α+ T cell numbers. Using protein biomarker analysis and an immunoassay, we detected in SAC–bone marrow co-cultures high levels of GM-CSF, IL-6, VEGF, IL-1β, TNFα, IL-10, and TGF-β. Furthermore, SAC-exposed neutrophils expressed Arg-1 and SAC-exposed monocytes expressed Arg-1 and iNOS, as shown via immunofluorescent stains. Overall, this study showed that SACs cause MDSC expansion from bone marrow cells and identified possible mediators to target as an additional strategy for treating chronic S. aureus infections.

scholarly journals In vivo modulation of myelopoiesis by prostaglandin E2. III. Induction of suppressor cells in marrow and spleen capable of mediating inhibition of CFU-GM proliferation

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1633-1640
Author(s):  
LM Pelus ◽  
PS Gentile
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Steady State ◽  
Prostaglandin E2 ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Spleen Cells ◽  
Granulocytic Differentiation ◽  
Marrow Cells

Intravenous (IV) injection of 0.1 to 10 micrograms of authentic prostaglandin E2 (PGE2) in intact steady-state mice induces a population of bone marrow and spleen cells having the capacity to suppress CFU-GM proliferation when admixed with normal bone marrow cells. Equivalent suppression of CFU-GM committed to monocytic as well as granulocytic differentiation was observed using colony-stimulating factors (CSFs) differing in their lineage specificities and by direct morphological analysis of proliferating clones. Kinetic analysis indicates that suppressive bone marrow cells appear within 2 hours after PGE2 injection, are maximal at 6 hours, and are no longer observed by 24 hours postinjection. Positive and negative selection studies using monoclonal antibodies indicate that the PGE2-induced suppressor cells react positively with anti-GMA 1.2, MAC1, and F4/80 monoclonal antibodies, suggesting a myeloid/monocytic origin. As few as 1,000 positively selected bone marrow or spleen cells were able to inhibit maximally normal CFU-GM proliferation by 50,000 control bone marrow cells. Suppression of normal CFU-GM can be substituted for by 24- hour cell-free supernates from unseparated bone marrow cells or GMA 1.2 or F4/80 positively selected marrow or spleen cells from PGE2-treated but not control mice. These supernates also inhibited BFU-E proliferation. Injection of as few as 2 million bone marrow cells from PGE2-treated mice into steady-state mice or animals hematopoietically rebounding following a sublethal injection of cyclophosphamide significantly suppressed total CFU-GM proliferation in recipient mice within 6 hours. In summary, these studies describe the detection of a novel hematopoietic control network induced by PGE2 in intact mice.

scholarly journals In vivo modulation of myelopoiesis by prostaglandin E2. III. Induction of suppressor cells in marrow and spleen capable of mediating inhibition of CFU-GM proliferation

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1633-1640 ◽  
Author(s):  
LM Pelus ◽  
PS Gentile
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Steady State ◽  
Prostaglandin E2 ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Spleen Cells ◽  
Granulocytic Differentiation ◽  
Marrow Cells

Abstract Intravenous (IV) injection of 0.1 to 10 micrograms of authentic prostaglandin E2 (PGE2) in intact steady-state mice induces a population of bone marrow and spleen cells having the capacity to suppress CFU-GM proliferation when admixed with normal bone marrow cells. Equivalent suppression of CFU-GM committed to monocytic as well as granulocytic differentiation was observed using colony-stimulating factors (CSFs) differing in their lineage specificities and by direct morphological analysis of proliferating clones. Kinetic analysis indicates that suppressive bone marrow cells appear within 2 hours after PGE2 injection, are maximal at 6 hours, and are no longer observed by 24 hours postinjection. Positive and negative selection studies using monoclonal antibodies indicate that the PGE2-induced suppressor cells react positively with anti-GMA 1.2, MAC1, and F4/80 monoclonal antibodies, suggesting a myeloid/monocytic origin. As few as 1,000 positively selected bone marrow or spleen cells were able to inhibit maximally normal CFU-GM proliferation by 50,000 control bone marrow cells. Suppression of normal CFU-GM can be substituted for by 24- hour cell-free supernates from unseparated bone marrow cells or GMA 1.2 or F4/80 positively selected marrow or spleen cells from PGE2-treated but not control mice. These supernates also inhibited BFU-E proliferation. Injection of as few as 2 million bone marrow cells from PGE2-treated mice into steady-state mice or animals hematopoietically rebounding following a sublethal injection of cyclophosphamide significantly suppressed total CFU-GM proliferation in recipient mice within 6 hours. In summary, these studies describe the detection of a novel hematopoietic control network induced by PGE2 in intact mice.

IMMU-05. CCR2+ MYELOID-DERIVED SUPPRESSOR CELLS FROM MURINE GLIOMAS ARE SOURCED FROM THE BONE MARROW, SUPPRESS T CELL ACTIVATION, AND MIGRATE TO CCL2

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi92-vi93
Author(s):  
Gregory Takacs ◽  
Christian Kreiger ◽  
Defang Luo ◽  
Joseph Flores-Toro ◽  
Loic Deleyrolle ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Bone Marrow Cells ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Wild Type ◽  
Suppressive Phenotype

Abstract INTRODUCTION Mounting evidence suggests infiltrating immune-suppressive cells contribute to immune checkpoint inhibitor resistance and poor survival in Glioblastoma (GBM) patients. We have previously shown glioma-associated monocytic-myeloid derived suppressor cells (M-MDSCs) express chemokine receptors CCR2 and CX3CR1. Genetic and pharmacologic targeting of CCR2 promoted sequestration of M-MDSCs in the bone marrow and, in combination with PD-1 blockade, slowed progression of KR158 and 005GSC murine gliomas. This combination treatment also enhanced infiltration of IFNg-producing T cells that were less exhausted. Although CCR2+/CX3CR1+ cells display surface markers indicative of bone marrow-derived M-MDSCs, additional studies are needed to formally establish the source of these cells and to determine if they exhibit an immune-suppressive phenotype as well as migrate to the CCR2 ligands, CCL2 and/or CCL7. OBJECTIVE Evaluate the source, migration, and immune suppressive function of CCR2+/CX3CR1+ myeloid cells from glioma bearing mice. METHODS To identify the source of CCR2+/CX3CR1+ myeloid cells, chimeric wild type mice harboring bone marrow cells from transgenic CCR2WT/RFP/CX3CR1WT/GFP mice were generated. CCR2+/CX3CR1+ cells were enriched from bone marrow obtained from either wild-type or CCR2WT/RFP/CX3CR1WT/GFP naïve and glioma-bearing mice in order to evaluate their immune suppressive phenotype and ability to migrate to CCL2 and CCL7. RESULTS CCR2+/CX3CR1+ cells are present in glioma isolates from chimeric mice, indicative of a bone marrow-derived cell population, and are detectable within the tumor microenvironment as early as 3 days post orthotopic implantation of KR158 cells; these cells accumulate as tumors increase in size (r=0.7605, p=0.007). CCR2+/CX3CR1+ M-MDSCs isolated from the bone marrow of tumor bearing mice suppress CD8+ T cell production of IFNg and migrate to CCL2 more efficiently than CCL7. CONCLUSION CCR2+/CX3CR1+ cells from glioma bearing mice are derived from the bone marrow and represent an immune suppressive population that migrates to CCL2.

scholarly journals Cellular basis of graft versus host tolerance in chimeras prepared with total lymphoid irradiation.

1980 ◽  
Vol 152 (3) ◽  
pp. 736-741 ◽  
Author(s):  
M Gottlieb ◽  
S Strober ◽  
H S Kaplan
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Third Party ◽  
Whole Body ◽  
Mixed Chimerism ◽  
Clonal Deletion ◽  
Donor Type ◽  
Host Tolerance ◽  
Marrow Cells

BALB/c mice given allogeneic (C57BL/Ka) bone marrow cells after toal lymphoid irradiation become stable chimeras approximately 80% donor-type and 20% host-type cells in the spleen. The chimeras doe not develop graft vs. host disease (GVHD). Purified cells of C57BL/Ka origin from the chimeras mediated GVHD in lightly irradiated C3H (third party), but not in BALB/c (host-strain) mice. Thus graft vs. host tolerance in the chimeras could not be explained by complete immunodeficiency of donor-type cells, serum blocking factors, or suppressor cells of host (BALB/c) origin. Clonal deletion or suppression of lymphocytes reactive with host tissues remain possible explanations. The transfer of donor-type chimeric spleen cells to BALB/c recipients given 500-550 rad whole-body irradiation WBI led to stable mixed chimerism in approximately 50% of recipients. The cells were presumably acting as tolerogens because similarly irradiated BALB/c mice given (BALB/c X C57BL/Ka)F1 spleen or bone marrow cells also became stable mixed chimeras.

scholarly journals Generation of CFU-C/suppressor T cells in vitro: an experimental model for immune-mediated marrow failure

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 491-496
Author(s):  
A Bacigalupo ◽  
M Podesta ◽  
MC Mingari ◽  
L Moretta ◽  
G Piaggio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Allogeneic Bone ◽  
Suppressor Activity ◽  
Healthy Donors ◽  
Marrow Cells

T cells were derived from the bone marrow of 8 healthy donors and fractionated, according to their receptors for the Fc fragment of IgG, into TG+ and TG- lymphocytes. These were then cocultured with autologous or allogeneic bone marrow cells in agar in the CFU-C assay. No significant suppresion of colony formation could be detected. Total T, TG+, and TG- cells were then incubated for 18 hr with PWM, washed, and cocultured with bone marrow cells. PWM-treated TG- cells showed no significant CFU-C suppressor activity, whereas PWM-treated total T and TG+ cells inhibited colony formation of both autologous and allogeneic marrow cells. The supernatant of PWM-treated total T and TG+ cells also inhibited colony formation. PWM alone enhanced colony formation. The results of this study indicate that normal T cells can be activated in vitro to become CFU-C/suppressor cells after PWM stimulation, and that this effect is mediated by T cells with the Fc receptor for IgG.

scholarly journals High Plasma Levels of Aβ1-42 Affect Monocytes and Macrophages via Biphasic Effects on Myeloid-Derived Suppressor Cells and Granulocyte-Monocyte Progenitors in Mouse Models of Alzheimer’s Disease

2021 ◽  
Author(s):  
Chunrong Li ◽  
Kangding Liu ◽  
Jie Zhu ◽  
Feiqi Zhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bone Marrow ◽  
Plasma Levels ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
High Plasma ◽  
Myeloid Derived Suppressor Cells ◽  
Monocytes And Macrophages ◽  
Inflammatory Macrophages

Abstract Background: Microglia play a crucial role in the pathogenesis of Alzheimer’s disease (AD). Plasma Aβ1-42 levels significantly increase 15 years before the onset of dominantly inherited AD. The effects of high plasma levels of Aβ1-42 on monocytes and macrophages, the hematogenous counterparts of microglia, remain unclear.Methods: We investigated the effects of plasma Aβ1-42 on peripheral monocytes and macrophages in three animal models, including 7- and 11-month-old female APPswe/PS1dE9 (APP/PS1) transgenic (Tg) mice, wild-type (Wt) parabiotic with Tg (paWt(Wt-Tg)) mice, and Wt mice.Results: We found that high plasma levels of Aβ1-42, in younger (7-month) AD mice significantly decreased the amounts of pro-inflammatory macrophages, myeloid derived suppressor cells (MDSCs), granulocyte-monocyte progenitors (GMP), and the plasma levels of interleukin-6 (IL-6). In older (11-month) AD mice, high plasma levels of Aβ1-42 significantly increased the amounts of pro-inflammatory macrophages, MDSCs, GMPs, the plasma levels of IL-6 and TNF-α, and the brain infiltration of bone marrow-derived macrophages (BMDMs). However, high plasma levels of Aβ1-42 consistently increased the amounts of monocytes and the proliferation of bone marrow cells (BMCs) without affecting the phagocytic function of macrophages on Aβ1-42.Conclusion: The response of mouse AD model suggests that a high plasma level of Aβ1-42 affects monocytes and macrophages via its biphasic effects on MDSCs and GMPs. We suggest that intervening in the effects of plasma Aβ1-42 on monocytes and macrophages might offer a new therapeutic approach to AD.

scholarly journals Generation of CFU-C/suppressor T cells in vitro: an experimental model for immune-mediated marrow failure

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 491-496 ◽  
Author(s):  
A Bacigalupo ◽  
M Podesta ◽  
MC Mingari ◽  
L Moretta ◽  
G Piaggio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Allogeneic Bone ◽  
Suppressor Activity ◽  
Healthy Donors ◽  
Marrow Cells

Abstract T cells were derived from the bone marrow of 8 healthy donors and fractionated, according to their receptors for the Fc fragment of IgG, into TG+ and TG- lymphocytes. These were then cocultured with autologous or allogeneic bone marrow cells in agar in the CFU-C assay. No significant suppresion of colony formation could be detected. Total T, TG+, and TG- cells were then incubated for 18 hr with PWM, washed, and cocultured with bone marrow cells. PWM-treated TG- cells showed no significant CFU-C suppressor activity, whereas PWM-treated total T and TG+ cells inhibited colony formation of both autologous and allogeneic marrow cells. The supernatant of PWM-treated total T and TG+ cells also inhibited colony formation. PWM alone enhanced colony formation. The results of this study indicate that normal T cells can be activated in vitro to become CFU-C/suppressor cells after PWM stimulation, and that this effect is mediated by T cells with the Fc receptor for IgG.

scholarly journals High Plasma Llevels of Aβ1-42 Affect Monocytes and Macrophages via Biphasic Effects on Myeloid-Derived Suppressor Cells and Granulocyte-Monocyte Progenitors in Mouse Models of Alzheimer’s Disease

2021 ◽  
Author(s):  
Chunrong Li ◽  
Kangding Liu ◽  
Jie Zhu ◽  
Feiqi Zhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bone Marrow ◽  
Plasma Levels ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
High Plasma ◽  
Myeloid Derived Suppressor Cells ◽  
Monocytes And Macrophages ◽  
Inflammatory Macrophages

Abstract Backgroud: Microglia play a crucial role in the pathogenesis of Alzheimer’s disease (AD). Plasma Aβ1-42 levels significantly increase 15 years before the onset of dominantly inherited AD. The effects of high plasma levels of Aβ1-42 on monocytes and macrophages, the hematogenous counterparts of microglia, remain unclear. Methods: We investigated the effects of plasma Aβ1-42 on peripheral monocytes and macrophages in three animal models, including 7- and 11-month-old female APPswe/PS1dE9 (APP/PS1) transgenic (Tg) mice, wild-type (Wt) parabiotic with Tg (paWt(Wt-Tg)) mice, and Wt mice. Results: We found that high plasma levels of Aβ1-42, in younger (7-month) AD mice significantly decreased the amounts of pro-inflammatory macrophages, myeloid derived suppressor cells (MDSCs), granulocyte-monocyte progenitors (GMP), and the plasma levels of interleukin-6 (IL-6). In older (11-month) AD mice, high plasma levels of Aβ1-42 significantly increased the amounts of pro-inflammatory macrophages, MDSCs, GMPs, the plasma levels of IL-6 and TNF-α, and the brain infiltration of bone marrow-derived macrophages (BMDMs). However, high plasma levels of Aβ1-42 consistently increased the amounts of monocytes and the proliferation of bone marrow cells (BMCs) without affecting the phagocytic function of macrophages on Aβ1-42. Conclusion: The response of mouse AD model suggests that a high plasma level of Aβ1-42 affects monocytes and macrophages via its biphasic effects on MDSCs and GMPs. We suggest that intervening in the effects of plasma Aβ1-42 on monocytes and macrophages might offer a new therapeutic approach to AD.

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