Figure 1.

Granulopoietic cells in the bone marrow. (A) From hematopoietic stem and pluripotent progenitor cells, to the mitotic pool of granulocyte precursors (myeloblasts, pro-mielocytes and myelocytes) and the post-mitotic pool of metamyelocytes, band cells and mature granulocytes. (B) Neutrophils are found in the bone marrow, blood (circulating pool), spleen, liver (marginated pool) and in tissues (transmigrated pool). Granulocyte colony-stimulating factor (G-CSF) induces the proliferation of granulocytic progenitors. CXCL1 and CXCL2 are constitutively expressed on endothelial cells of the BM, whereas osteoblasts are the major source of CXCL12. G-CSF regulate the traffic of neutrophils: CXCR4 and its ligand CXCL12 (SDF-1) mediate neutrophil retention in the bone marrow, while CXCR2 and their ligands CXCL1 e CXCL2 promote neutrophil release, contributing for the circulating neutrophil pool. G-CSF enhances the release of neutrophils by inhibiting CXCR4/CXCL12. In physiological conditions, neutrophils in the circulating pool and in the marginated pool are in almost equivalent proportions. Neutrophils in the peripheral blood can be recruited into peripheral tissues (transmigrating pool). During inflammation, the inflammatory mediators released in peripheral tissues can act locally, inducing neutrophil recruitment into peripheral tissue; and, at distance, inducing neutrophil mobilization from the bone marrow, where the concentration of CXCR2 ligands increases, while CXCL12 expression decreases, allowing increased neutrophil migration.