Figure 1.

Neutrophil homeostasis is tightly regulated. In homeostatic conditions (black arrows) neutrophils mature in the bone marrow from undifferentiated hematopoietic stem cells (HSCs), replenishing the mitotic stem cell pool that gives rise to mature neutrophils via different immature stages of myeloblast, promyelocyte, myelocyte, metamyelocyte, immature band cells, and mature neutrophils. These neutrophils are stored in the bone marrow upon release before entering the blood circulation. Different organs store a pool of neutrophils, referred to as marginated pool, and are forming a reservoir of mature neutrophils. In response to inflammation, neutrophils can exit the bloodstream and enter the tissue pool. Senescent neutrophils are cleared in the bone marrow by stromal macrophages or by tissue-resident macrophages in the periphery. During excessive inflammation (red arrows), neutrophils are massively attracted to the site of inflammation and their clearance is decreased by increasing their lifespan. Demanding the high need for neutrophils, increased numbers of neutrophils are released from the bone marrow. Furthermore, neutrophils are formed and released from extramedullary sites. Cytokine stimulation, including epinephrine, can additionally quickly release neutrophils from the marginated pool.