Abstract
BackgroundGranulocytes and monocytes/macrophages differentiate from common myeloid progenitor cells. Granulocyte colony-stimulating factor (G-CSF) and CD137 (4-1BB, TNFRSF9) are growth and differentiation factors that induce granulocyte and macrophage survival and differentiation, respectively. This study describes the influence of G-CSF and recombinant CD137-Fc protein on myelopoiesis.Methodology/Principal FindingsBoth, G-CSF and CD137 protein support proliferation and survival of murine bone marrow cells. G-CSF enhances granulocyte numbers while CD137 protein enhances macrophage numbers. Both growth factors together give rise to more cells than each factor alone. Titration of G-CSF and CD137 protein dose-dependently changes the granulocyte/macrophage ratio in bone marrow cells. Both factors individually induce proliferation of hematopoietic progenitor cells (lin-, c-kit+) and differentiation to granulocytes and macrophages, respectively. The combination of G-CSF and CD137 protein further increases proliferation, and results in a higher number of macrophages than CD137 protein alone, and a lower number of granulocytes than G-CSF alone demonstrating that CD137 protein-induced monocytic differentiation is dominant over G-CSF-induced granulocytic differentiation. CD137 protein induces monocytic differentiation even in early hematopoietic progenitor cells, the common myeloid progenitors and the granulocyte macrophage progenitors.Conclusions/SignificanceThis study confirms earlier data on the regulation of myelopoiesis by CD137 receptor - ligand interaction, and extends them by demonstrating the restriction of this growth promoting influence to the monocytic lineage.
Highlights
IntroductionAs neutrophil and eosinophil granulocytes they form the first defense line against bacteria and multicellular parasites, respectively
Granulocytes are essential cells of the innate immune system
We find that treatment of total murine bone marrow cells with recombinant CD137 protein enhances the percentage of myeloid cells except that of granulocytes
Summary
As neutrophil and eosinophil granulocytes they form the first defense line against bacteria and multicellular parasites, respectively. Through release of their cytotoxic and inflammatory mediators granulocytes participate in the elimination of pathogens, recruitment of additional immune cells and perpetuation of the inflammatory reaction [1]. At sites of inflammation proinflammatory cytokines such as GCSF, granulocyte macrophage colony-stimulating factor (GMCSF), tumor necrosis factor (TNF) and interferon (IFN)-c extend the life span of granulocytes by preventing apoptosis [2,3]. Granulocytes and monocytes/macrophages differentiate from common myeloid progenitor cells. Granulocyte colony-stimulating factor (G-CSF) and CD137 (4-1BB, TNFRSF9) are growth and differentiation factors that induce granulocyte and macrophage survival and differentiation, respectively. This study describes the influence of G-CSF and recombinant CD137-Fc protein on myelopoiesis
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