29/02/2020
LIFECYCLE OF HUMAN NEUTROPHILS
The life cycle of neutrophils presents substantial molecular and phenotypic heterogeneity.
Neutrophils arise in bone marrow, spleen and lung from hematopoietic stem cells (HSC), progressing to committed granulocyte-monocyte progenitors (GMP), and then through a set of intermediate stages to mature neutrophils. Neutrophils exit to blood under the control of CXCR2, usually as mature cells but under conditions of stress also as immature cells. Over time, neutrophils age, expressing CXCR4 that mediates return to marrow. Alternate pathways for blood neutrophils include intravascular activation, intravascular margination, homeostatic migration into tissues, or migration into inflamed tissues. Clearance occurs via macrophages either in tissues or in bone marrow. The localization of the recently-defined preNeu in the previously-accepted neutrophil ontology (GMP → myeloblast → promyelocyte → myelocyte) remains uncertain. The small circular arrow ↺ reflects replication competence.
Mature human neutrophils exhibit a characteristic multilobular nucleus and high surface expression of CD16 (FcγRIII), CD62L (L-selectin), and CD10 (neutral endopeptidase), along with neutrophil lineage markers CD15 and CD66b. By contrast, immature neutrophils released from marrow after immune stress are CD16 low and CD10 low, often but not invariably together with band nuclear morphology. Neutrophils less mature than band cells exhibit elevated CD33 and lower CXCR2, the receptor that enables mobilization out of the bone marrow niche. Immature neutrophils express more CXCR4 than mature neutrophils, likely promoting their retention in the bone marrow. As neutrophils age, expression of CXCR4 again increases, licensing return to the bone marrow for clearance. Aging is accompanied by other changes, including elevated expression of the integrins CD11b and CD11c, lower CD62L, and lower CD47, an inhibitor of phagocytosis.
If you found this information interesting, share it on your networks and so we grow together!
Regards!
Carlos Manuel Llanos Albornoz
Director, Hematology World Foundation