Homeostatic regulation of blood neutrophil counts.
Blood neutrophil counts are determined by the differentiation and proliferation of precursor cells, the release of mature neutrophils from the bone marrow, margination, trafficking and transmigration through the endothelial lining, neutrophil apoptosis, and uptake by phagocytes. This brief review summarizes the regulation of blood neutrophil counts, which is in part controlled by G-CSF, IL-17, and IL-23. Neutrophils are retained in the bone marrow through interaction of CXCL12 with its receptor CXCR4. The relevance of this mechanism is illustrated by rare diseases in which disrupting the desensitization of CXCR4 results in failure to release mature neutrophils from bone marrow. Although blood neutrophil numbers in inbred mouse strains and individual human subjects are tightly controlled, their large variation among outbred populations suggests genetic factors. One example is benign ethnic neutropenia, which is found in some African Americans. Reduced and elevated neutrophil counts, even within the normal range, are associated with excess all-cause mortality.
von Vietinghoff
Sibylle
S
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Ley
Klaus
K
D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D042381:Granulocyte Precursor Cells / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D007958:Leukocyte Count; D051379:Mice; D009503:Neutropenia / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor