Figure 2. The Mammalian Neutrophil Feedback Loop.

Following exertion of their functions in the liver, neutrophils pass through the lung to return to the bone marrow. The invasion and extravasation of neutrophils into and from the bone marrow relies on CXCR4 and CXCR2 dependent signaling cues. CXC-motif chemokine receptor (CXCR) 4 high neutrophils get cleared from the circulation in the bone marrow. At the same time, CXCR4 is responsible for the maintenance of the marginated pool in the lung and the regress of neutrophils into the bone marrow. CXCR2 leads to mobilization of neutrophils from the bone marrow niche. In a cancer environment, protumorigenic neutrophils are released from the bone marrow and sent to the lung. In an inflammatory setting, neutrophils modulate the hematopoietic stem and progenitor cell environment in the bone marrow by releasing of prostaglandin E₂. Neutrophils returning into the bone marrow can be emperipolized by megakaryocytes. Emperipolesis describes a process in which neutrophils are “ingested” by megakaryocytes without phagocytosing the cell. This step leads to the transfer of membrane fragments from neutrophils to newly produced platelets, possibly resulting in a population of ‘inflammatory’ platelets. Neutrophils can then return into circulation and exert their functions again. Bacteria; Neutrophil; Platelets; Megakaryocyte