RT Book, Section A1 Smith, C. Wayne A2 Kaushansky, Kenneth A2 Lichtman, Marshall A. A2 Prchal, Josef T. A2 Levi, Marcel M. A2 Press, Oliver W. A2 Burns, Linda J. A2 Caligiuri, Michael SR Print(0) ID 1121095526 T1 Production, Distribution, and Fate of Neutrophils T2 Williams Hematology, 9e YR 2015 FD 2015 PB McGraw-Hill Education PP New York, NY SN 9780071833004 LK hemonc.mhmedical.com/content.aspx?aid=1121095526 RD 2024/03/29 AB SUMMARYBlood neutrophil levels are maintained in a normal steady state by hematopoiesis in the marrow, the distribution of neutrophils between the marginated pool in the microvasculature and the freely circulating pool in the blood, and the rate of egress from blood to tissues. Marrow production of neutrophils is regulated by three principal glycoprotein hormones, or cytokines: interleukin-3, granulocyte-monocyte colony-stimulating factor, and granulocyte colony-stimulating factor (G-CSF), but only the genetic elimination of G-CSF has a measurable effect on blood neutrophil levels. The latter two cytokines are available as recombinant pharmaceutical products that can be administered therapeutically to ameliorate certain causes of neutropenia. Neutrophil interaction with endothelium is mediated by selectins, glycoproteins with sugar-binding sites that support shear-dependent rolling on endothelium, and by integrins on the neutrophil binding to ligands on the endothelial cells, permitting firm attachment to endothelium and emigration into tissues. Neutrophils have a short life span in blood, with a disappearance half-time of approximately 7 hours. The process can be accelerated when inflammation is present and highlights the need for a sustained rate of production to maintain a normal blood neutrophil count. The pathogenesis of neutropenia is more complex to analyze kinetically than anemia or thrombocytopenia because at least four compartments are involved: marrow storage pool, circulating pool, marginated pool, and tissue pool. The latter is particularly difficult to assay. Measurements can be further complicated in the nonsteady state, when dramatic increases in turnover rates and distribution among the four principal pools are in disequilibrium, as occurs during acute inflammatory states.