**2. Synthesis and production of neutrophils cells**

Neutrophil production and synthesis is a major activity of the bone marrow. In fact, two-thirds of blood cell synthesis in bone marrow is dedicated to the production of monocytes and granulocytes. Hematopoietic stem cells are characterized by little blood flow and low oxygen tension, while the more mature and actively dividing stem cells reside closer to the abluminal

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side of the sinusoids, the special vascular structure of the bone marrow. The chemokine receptor CXCR4 is essential for the homing of stem cells and more mature neutrophils to the bone marrow [6].

Deletion of CXCR4 causes mature neutrophils to be released from the bone marrow into circulation without affecting the life-span of circulating neutrophils [6, 7].

The production of neutrophils is extensive, with 1 - 2 × 1011 cells being generated per day in a normal adult human. Granulocyte colony stimulating factor (G-CSF) is essential for tuning the production of neutrophils to meet the increased needs that occur during infections, but G-CSF is not absolutely required for granulocytopoiesis. Indeed, G-CSF null mice have approximately 25% residual granulocytopoiesis and still generate fully mature neutrophils [6]. The produc‐ tion of neutrophils is largely regulated by the rate of apoptosis of neutrophils in tissues. When macrophages and dendritic cells phagocytose apoptotic neutrophils in tissues, the production of interleukin 23 (IL-23) is reduced [6].
