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Granulopoiesis (or granulocytopoiesis) is a part of haematopoiesis, that leads to the production of granulocytes. A granulocyte, also referred to as polymorphonuclear lymphocyte (PMN), is a type of white blood cell that has multi lobed nuclei, usually containing three lobes, and has a significant amount of cytoplasmic granules within the cell. [1] Granulopoiesis takes place in the bone marrow. [2] And leads to production of three types of mature granulocytes: neutrophils (most abundant, making up to 60 % of all white blood cells), eosinophils (up to 4 %) and basophils (up to 1 %).[3]

Stages of granulocyte development[edit]

Granulopoiesis is often divided into two parts - granulocyte lineage determination, which involves all the early maturation steps that might be common for all myeloid cells and commited granulopoiesis, which is the irreversible commitment to become a granulocyte. [4]

Granulocyte lineage determination[edit]

Granulopoiesis, as well as the rest of haematopoiesis, begins from a haematopoietic stem cells. These are multipotent cells that reside in the bone marrow niche and have the ability to give rise to all heamatopoetic cells, as well as the ability of self renewal. They give rise to either a common lymphoid progenitor (CLP, a progenitor for all lymphoid cells) or a common myeloid progenitor, CMP, an oligopotent progenitor cell, that gives rise to the myeloid part of the heamatopoetic tree. [2] The first stage of the myeloid lineage is a granulocyte - monocyte progenitor (GMP), sill an oligopotent progenitors, which then develops into unipotent cells that will later on form population of granulocytes, as well as monocytes. The first unipotent cell in granulopoiesis is a myeloblast. [5]

Commited granulopoiesis[edit]

Commited granulopoiesis is comprised of maturation stages of unipotent cell. It starts with the first cell that starts to resemble a granulocyte - a myeloblast. It is characterized by large oval nucleus that takes up most of the space in the cell and a very little cytoplasm. The next developmental stage - a promyelocyte still has a large oval nucleus, but it has more cytoplasm than a myeloblast, also cytoplasmic granules are beggining to form at this stage. The development of granules is continuing with the next stage - a myelocyte, the nucleus is also starting to shrink at this point. At a stage of metamyelocyte the cell nucleus is starting to become kidney-shaped and it becomes even more bent in the stage of a band cell. The maturation is finished with the emergence of a segmented nucleus, that is specific for a mature granulocyte. [6]

Regulation of granulopoiesis[edit]

Transcriptional regulation[edit]

The maturation of granulocytic precursors is tightly regulated at transcriptional level. Granulocyte lineage determination is regulated by expression of C/EBPα, which is necessary for the transition from CMPs to GMPs and levels of PU.1 which decide if GMPs are going to produce mostly monocytes (high PU.1 levels) or granulocytes (low PU.1 levels). Commited granulopoiesis is regulated by C/EBPε GFI-1, these two transcriptional factors are important for terminal granulocyte differentiation. Other trancriptional factors that play role in granulopoiesis are: CBF, MYB, SMAD4 and HOX genes. [1] [7]

Regulation by cytokines[edit]

Granulopoiesis is also regulated by cytokines to a certain extent. The main cytokines driving granulopoiesis are: GM-CSF (formation of GMP from CMP), G-CSF (commitment to the granulocyte lineage, formation of myeloblasts from GMP), IL-3 (enhances the production of GM-CSF and G-CSF) [8] and SCF. These are secreted by other haematopoietic cells in the bone marrow or at the site of inflammation. [9]

Types of granulopoiesis[edit]

Steady state granulopoiesis[edit]

Steady state granulopoiesis is a term used to describe the normal daily production of granulocytes. Granulocytes are short lived cells (their lifespan is between 6 and 8 hours) with a high cell turnover. The number of granulocytes produced every day is between 5 and 10 x 1010. [10] The master regulator of steady state granulopoiesis, C/EBPα, inhibits CDK2 and CDK4 and therefore restricts the cell cycle of immature cells and promotes granulocytic differentiation. [11] It is activated after the engulfment of apoptotic granulocytes by tissue macrophages.[12]

Emergency granulopoiesis[edit]

Steady state granulopoiesis is switched to a programme termed emergency granulopoiesis after a major insult to the organism, usually a bacterial infection. The switch of the programmes is mediated by switch from C/EBPα to C/EBPβ, the main transcriptional regulator of emergency granulopoiesis. It enhances the production of granulocytes by promoting progression of the cell cycle of myeloid progenitors at accelerated rate, therefore generating sufficient amount of new granulocyte to fight the insult. [11] [13]


  1. ^ a b Cowland, Jack B.; Borregaard, Niels (09 2016). "Granulopoiesis and granules of human neutrophils". Immunological Reviews. 273 (1): 11–28. doi:10.1111/imr.12440. ISSN 1600-065X. PMID 27558325. {{cite journal}}: Check date values in: |date= (help)
  2. ^ a b Morrison, Sean J.; Scadden, David T. (2014-01). "The bone marrow niche for haematopoietic stem cells". Nature. 505 (7483): 327–334. doi:10.1038/nature12984. ISSN 1476-4687. {{cite journal}}: Check date values in: |date= (help)
  3. ^ Blumenreich, Martin S. (1990), Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis (eds.), "The White Blood Cell and Differential Count", Clinical Methods: The History, Physical, and Laboratory Examinations (3rd ed.), Butterworths, ISBN 978-0-409-90077-4, PMID 21250104, retrieved 2020-01-23
  4. ^ Cowland, Jack B.; Borregaard, Niels (2016-09). "Granulopoiesis and granules of human neutrophils". Immunological Reviews. 273 (1): 11–28. doi:10.1111/imr.12440. {{cite journal}}: Check date values in: |date= (help)
  5. ^ Doulatov, Sergei; Notta, Faiyaz; Laurenti, Elisa; Dick, John E. (2012-02-03). "Hematopoiesis: A Human Perspective". Cell Stem Cell. 10 (2): 120–136. doi:10.1016/j.stem.2012.01.006. ISSN 1934-5909. {{cite journal}}: no-break space character in |first4= at position 5 (help)
  6. ^ Wahed, Amer; Dasgupta, Amitava (2015-01-01), Wahed, Amer; Dasgupta, Amitava (eds.), "Chapter 2 - Bone Marrow Examination and Interpretation", Hematology and Coagulation, Elsevier, pp. 15–29, ISBN 978-0-12-800241-4, retrieved 2020-01-26
  7. ^ Ward, A. C.; Loeb, D. M.; Soede-Bobok, A. A.; Touw, I. P.; Friedman, A. D. (2000-06). "Regulation of granulopoiesis by transcription factors and cytokine signals". Leukemia. 14 (6): 973–990. doi:10.1038/sj.leu.2401808. ISSN 1476-5551. {{cite journal}}: Check date values in: |date= (help)
  8. ^ T, Tsuji; K, Sugimoto; T, Yanai; E, Takashita; Kj, Mori (1994). "Induction of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and Granulocyte Colony-Stimulating Factor (G-CSF) Expression in Bone Marrow and Fractionated Marrow Cell Populations by Interleukin 3 (IL-3): IL-3-mediated Positive Feedback Mechanisms of Granulopoiesis". Growth factors (Chur, Switzerland). PMID 7530467. Retrieved 2020-01-26.
  9. ^ Kawahara, Rodney (2007-01-01), Enna, S. J.; Bylund, David B. (eds.), "Leukopoiesis", xPharm: The Comprehensive Pharmacology Reference, Elsevier, pp. 1–5, ISBN 978-0-08-055232-3, retrieved 2020-01-26
  10. ^ Summers, Charlotte; Rankin, Sara M.; Condliffe, Alison M.; Singh, Nanak; Peters, A. Michael; Chilvers, Edwin R. (2010-8). "Neutrophil kinetics in health and disease". Trends in Immunology. 31 (8): 318–324. doi:10.1016/j.it.2010.05.006. ISSN 1471-4906. PMC 2930213. PMID 20620114. {{cite journal}}: Check date values in: |date= (help)
  11. ^ a b Manz, Markus G.; Boettcher, Steffen (2014-05). "Emergency granulopoiesis". Nature Reviews Immunology. 14 (5): 302–314. doi:10.1038/nri3660. ISSN 1474-1733. {{cite journal}}: Check date values in: |date= (help)
  12. ^ Lawrence, Shelley M.; Corriden, Ross; Nizet, Victor (2018-03-01). "The Ontogeny of a Neutrophil: Mechanisms of Granulopoiesis and Homeostasis". Microbiology and Molecular Biology Reviews. 82 (1). doi:10.1128/MMBR.00057-17. ISSN 1092-2172. PMC 5813886. PMID 29436479.{{cite journal}}: CS1 maint: PMC format (link)
  13. ^ Hirai, Hideyo; Zhang, Pu; Dayaram, Tajhal; Hetherington, Christopher J; Mizuno, Shin-ichi; Imanishi, Jiro; Akashi, Koichi; Tenen, Daniel G (2006-07). "C/EBPβ is required for 'emergency' granulopoiesis". Nature Immunology. 7 (7): 732–739. doi:10.1038/ni1354. ISSN 1529-2908. {{cite journal}}: Check date values in: |date= (help)
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