Integration of factors determining neutrophil lifespan. The bone marrow neutrophil lineage is composed of 3 compartments: (1) the hematopoietic stem cell (HSC) pool, (2) the mitotic pool that is comprised of myeloblasts, promyelocytes, and myelocytes, and (3) the postmitotic pool that is comprised of metamyelocytes, band cells, and mature neutrophils. The size of the mitotic and postmitotic pool is estimated at 4.36 × 109 and 8.8 × 109 cells/kg, respectively. After 4 to 6 days in the bone marrow, neutrophils are released to the bloodstream (4.3-4.5 × 109 cells/L). The estimated period of time where neutrophils circulate is controversial. Although some studies suggest that the circulating lifespan is around 5 hours, alternative experimental calculation raises neutrophil lifespan up to 5.4 days, as reported in different studies. Neutrophils are also located in the “marginated pools,” vascular pools located in the lungs, spleen, and liver where the turnover time is still unclear. After neutrophils infiltrate tissues during inflammation, interaction with tissue-derived signals such as cytokines, PAMPs, DAMPs, or environmental factors reduces neutrophil apoptosis and increases their lifespan to an extent that remains unknown. fMLF, formyl-methionyl-leucyl phenylalanine; HMGB1, high-mobility group box-1.
