Related Experiment Video
Updated: Aug 20, 2026

Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
Macrophage derived signalling regulates negatively the megakaryocyte compartment
V I Landoni1, M Vermeulen, N Van Rooijen
1Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Abstract:
Megakaryocytopoiesis is the process by which stem cells go through a process of commitment, proliferation and differentiation leading to the production of platelets. In the mouse, this process is accomplished within the bone marrow (BM) and spleen microenvironment and is carried out by regulatory molecules and accessory cells including macrophages, fibroblasts and endothelial-like cells. Previously, we have reported that macrophage depletion following administration of liposomal clodronate (LIP-CLOD) provokes enhancement of both, megakaryocytopoiesis and thrombocytopoiesis. In this report, we investigated the changes in the compartment of megakaryocyte progenitor cells (MK-CFU), their correlation with plasmatic thrombopoietin (TPO) and TPO transcription levels after macrophage depletion. LIP-CLOD-treated mice showed an increase of the MK-CFU in BM and spleen. Concerning TPO plasma levels, kinetic studies revealed a 1.5- and 1.3-fold increase in the TPO concentration at 12 and 24 hr of treatment. We also show evidence of regulation of TPO transcription in the liver and spleen. Although empty liposomes also enhanced TPO gene regulation in these organs, transcriptional TPO up regulation correlated with an increase of protein synthesis only in those animals where macrophages were effectively removed. Taken together, these results suggest that BM and spleen macrophages derived signalling regulates negatively the megakaryocyte compartment.
Insights
Depleting macrophages enhances megakaryocyte progenitor cells (MK-CFU) and thrombopoietin (TPO) levels. Macrophage signaling negatively regulates megakaryocytopoiesis in the bone marrow and spleen.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Megakaryocytopoiesis, the production of platelets from stem cells, occurs in the bone marrow and spleen microenvironments.
- Accessory cells, including macrophages, play regulatory roles in megakaryocytopoiesis.
- Previous studies indicated that macrophage depletion enhances megakaryocytopoiesis and thrombocytopoiesis.
Purpose of the Study:
- To investigate the impact of macrophage depletion on megakaryocyte progenitor cells (MK-CFU) and thrombopoietin (TPO) levels.
- To explore the correlation between MK-CFU, plasma TPO, and TPO transcription levels following macrophage depletion.
- To elucidate the role of bone marrow and spleen macrophages in regulating the megakaryocyte compartment.
Main Methods:
- Macrophage depletion was induced using liposomal clodronate (LIP-CLOD) in mice.
- Quantification of megakaryocyte progenitor cells (MK-CFU) in bone marrow and spleen.
- Measurement of plasma thrombopoietin (TPO) levels over time.
- Analysis of TPO transcription levels in the liver and spleen.
Main Results:
- LIP-CLOD treatment significantly increased MK-CFU in both bone marrow and spleen.
- Plasma TPO concentrations showed a 1.5-fold and 1.3-fold increase at 12 and 24 hours post-treatment, respectively.
- TPO gene regulation was observed in the liver and spleen, with transcriptional upregulation correlating with increased protein synthesis only upon effective macrophage removal.
Conclusions:
- Macrophage depletion leads to an increase in megakaryocyte progenitor cells and thrombopoietin levels.
- Bone marrow and spleen macrophages negatively regulate megakaryocytopoiesis through signaling pathways.
- Targeting macrophages may represent a therapeutic strategy to modulate platelet production.
Related Concept Videos
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Differentiation of Common Myeloid Progenitor Cells
Autocrine Signaling
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
Amplifying Signals via Enzymatic Cascade
The JAK-STAT Signaling Pathway

