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Markers of Granulocytic Maturation

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P322

2026-02-05

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Stem cells have been characterized primarily by their marrow repopulating potential, as outlined in Chapter 9. Early granulocytic progenitors form hematopoietic colonies in vitro and their more differentiated progeny express specific cell surface proteins that are critically important to myeloid differentiation and function. They mediate both the adhesion of precursors within the BM and the vascular adhesion of mature neutrophils needed for normal neutrophil activation. Other proteins serve as receptors that recognize pathogens or as stimulatory peptides that facilitate activation of phagocytosis and killing of organisms. Appropriate expression of these surface proteins plays an important role in normal neutrophil function, and abnormalities of their expression are implicated in a wide range of diseases affecting the neutrophil compartment. For example, congenital abnormalities in the surface expression of integrin proteins are responsible for failure of neutrophil adhesion in leukocyte adhesion deficiency, whereas acquired abnormalities of expression of the same proteins are thought to underlie the abnormal circulation of immature precursors in myeloproliferative neoplasms.1 These markers also serve to help distinguish among the stages of myeloid commitment and maturation.

The phenotype of the early hematopoietic stem cells is CD34+CD38−CD33−, with absence of lineage-specific markers. The common myeloid progenitor, colony-forming unit–granulocyte erythrocyte–macrophage–megakaryocyte (CFU-GEMM), is char acterized by the coexpression of CD33. CD33 is expressed at high levels on committed myeloid progenitors and on early precursors of both the granulocytic and monocytic lineages. Expression of CD33 wanes with granulocytic maturation and is absent or nearly absent beyond the myelocyte stage. CD33 is a member of the sialic acid binding immunoglobulin (Ig)-like lectins (siglecs), which mediate cell-cell interactions and cell signaling pathways involved in immune responses and inflammation. This class of receptors recognizes endogenous sialoglycans as “self-associated molecular patterns” (SAMPs), dampening immune responses via cytosolic Src homology-2 (SH2) domain–containing protein tyrosine phosphatase 1 (SHP1) and SHP2 tyrosine phosphatases and the suppressor of cytokine signaling 3 (SOCS3).

Characteristic granulocyte markers acquired as the early myeloid progenitor cells become committed to the neutrophil lineage include CD45RA, MPO, and CD38, all of which are expressed by myeloblasts. Further differentiation beyond the myelocyte stage is associated with expression of CD16, CD11b/CD18 (Mac-1), and leukocyte alkaline phosphatase (LAP), all of which are expressed at high levels in mature neutrophils.