Neutrophils: Need for Standardized Nomenclature

Abstract

Neutrophils are the most abundant innate immune cell with critical anti-microbial functions. Since the discovery of granulocytes at the end of the nineteenth century, the cells have been given many names including phagocytes, polymorphonuclear neutrophils (PMN), granulocytic myeloid derived suppressor cells (G-MDSC), low density neutrophils (LDN) and tumor associated neutrophils (TANS). This lack of standardized nomenclature for neutrophils suggest that biologically distinct populations of neutrophils exist, particularly in disease, when in fact these may simply be a manifestation of the plasticity of the neutrophil as opposed to unique populations. In this review, we profile the surface markers and granule expression of each stage of granulopoiesis to offer insight into how each stage of maturity may be identified. We also highlight the remarkable surface marker expression profiles between the supposed neutrophil populations.

Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights

“…Neutrophils, ascribed as warriors against pathogens and critical actors in the innate immune system with high pro-inflammatory activity constitute the dominant immune cell population in human blood with ~10 11 neutrophils generated every day in the bone marrow ( 24 , 25 ). They are the first responders to infection and inflammation, providing a key pivot between resolution or propagation of collateral damage that can result in multi-system organ failure.…”

“…These cells are endowed with huge microbicidal potential by virtue of their phagocytic capacity, ability to produce reactive oxygen intermediates, a rich array of granule-derived lytic enzymes and a tendency to release neutrophil extracellular traps (NETs). A vast body of literature shows that neutrophil dysfunction can contribute significantly to sepsis and a variety of autoimmune diseases ( 24 , 26 , 27 ). Neutrophils can promote cancer progression by facilitating matrix remodeling, stimulating angiogenesis, and by disabling T-cell-dependent antitumor immunity ( 28 ).…”

Immunosuppression Affects Neutrophil Functions: Does Calcineurin-NFAT Signaling Matter?

“…LDNs from these patients may also show profound functional alterations, for example in systemic lupus erythematosus where LDN exhibit enhanced spontaneous NETosis and relatively higher mitochondrial ROS production when compared to NDN ex vivo (44). In patients with cancer, circulating LDNs display marked immunosuppressive and protumorigenic activities, similar to those documented for tumorassociated neutrophils (45)(46)(47).…”

“…Recent studies looking at immunosuppressive neutrophils have uncovered a potential candidate LDN subpopulation but have yet to agree on a unified terminology: these cells are variously termed “granulocytic-” or “polymorphonuclear- myeloid-derived suppressor cells” (G-MDSCs or PMN-MDSCs) ( 47 , 48 , 51 ). Although studies of these cells are in their infancy, we know that PMN-MDSCs often contain immature neutrophils ( 48 , 52 , 53 ) and are observed in patients with sepsis or fungal infections caused by Aspergillus fumigatus (A. fumigatus) or Candida albicans ( C. albicans) ( 54 , 55 ).…”

“…Ex vivo , PMN-MDSCs from these patients inhibit T-cell proliferation and IFN-γ production via ROS or arginase-1 production ( 48 , 54 , 55 ). Identifying PMN-MDSCs among LDNs has been challenging as there is a lack of a defined, consensus surface molecule expression panel that can distinguish between the two ( 38 , 47 ). However, it is possible to confirm MDSCs’ identity functionally, through their ability to suppress immune responses (e.g.…”