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Structural and functional diversity of neutrophil glycosylation in innate immunity and related disorders
The granulated neutrophils are abundant innate immune cells that utilize bioactive glycoproteins packed in cytosolic granules to fight pathogenic infections, but the neutrophil glycobiology remains poorly understood. Facilitated by technological advances in glycoimmunology, systems glycobiology and...
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Published in: | Molecular aspects of medicine 2021-06, Vol.79, p.100882-100882, Article 100882 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The granulated neutrophils are abundant innate immune cells that utilize bioactive glycoproteins packed in cytosolic granules to fight pathogenic infections, but the neutrophil glycobiology remains poorly understood. Facilitated by technological advances in glycoimmunology, systems glycobiology and glycoanalytics, a considerable body of literature reporting on novel aspects of neutrophil glycosylation has accumulated. Herein, we summarize the building knowledge of the structural and functional diversity displayed by N- and O-linked glycoproteins spatiotemporally expressed and sequentially brought-into-action across the diverse neutrophil life stages during bone marrow maturation, movements to, from and within the blood circulation and microbicidal processes at the inflammatory sites in peripheral tissues. It transpires that neutrophils abundantly decorate their granule glycoproteins including neutrophil elastase, myeloperoxidase and cathepsin G with peculiar glyco-signatures not commonly reported in other areas of human glycobiology such as hyper-truncated chitobiose core- and paucimannosidic-type N-glycans and monoantennary complex-type N-glycans. Sialyl Lewisx, Lewisx, poly-N-acetyllactosamine extensions and core 1-/2-type O-glycans are also common neutrophil glyco-signatures. Granule-specific glycosylation is another fascinating yet not fully understood feature of neutrophils. Recent literature suggests that unconventional biosynthetic pathways and functions underpin these prominent neutrophil-associated glyco-phenotypes. The impact of glycosylation on key neutrophil effector functions including extravasation, degranulation, phagocytosis and formation of neutrophil extracellular traps during normal physiological conditions and in innate immune-related diseases is discussed. We also highlight new technologies that are expected to further advance neutrophil glycobiology and briefly discuss the untapped diagnostic and therapeutic potential of neutrophil glycosylation that could open avenues to combat the increasingly prevalent innate immune disorders.
•Maturing neutrophils pack bioactive glycoproteins in releasable cytosolic granules.•Unconventional glycan structures and biosynthetic pathways exist in neutrophils.•Paucimannose and chitobiose core glycans are examples of key neutrophil signatures.•The granule glycoproteins are brought into action via staged degranulation.•Glycans mediate neutrophil functions e.g. movement, pathogen killing, communication. |
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ISSN: | 0098-2997 1872-9452 |
DOI: | 10.1016/j.mam.2020.100882 |