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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. Granulopoiesis takes place in the bone marrow. 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 %).

Stages of granulocyte development
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.

Granulocyte lineage determination
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. 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 granulocyte s, as well as monocytes. The first unipotent cell in granulopoiesis is a myeloblast.

Commited granulopoiesis
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.

Transcriptional regulation
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.

Regulation by cytokines
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) and SCF. These are secreted by other haematopoietic cells in the bone marrow or at the site of inflammation.

Steady state granulopoiesis
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. 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. It is activated after the engulfment of apoptotic granulocytes by tissue macrophages.

Emergency granulopoiesis
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.