Reactome | Neutrophil degranulation

Neutrophil degranulation

Stable Identifier

R-HSA-6798695

DOI

10.3180/R-HSA-6798695.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Neutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and migrate towards the inflammatory focus. They contain several subsets of granules that are mobilized to fuse with the cell membrane or phagosomal membrane, resulting in the exocytosis or exposure of membrane proteins. Traditionally, neutrophil granule constituents are described as antimicrobial or proteolytic, but granules also introduce membrane proteins to the cell surface, changing how the neutrophil responds to its environment (Borregaard et al. 2007). Primed neutrophils actively secrete cytokines and other inflammatory mediators and can present antigens via MHC II, stimulating T-cells (Wright et al. 2010).

Granules form during neutrophil differentiation. Granule subtypes can be distinguished by their content but overlap in structure and composition. The differences are believed to be a consequence of changing protein expression and differential timing of granule formation during the terminal processes of neutrophil differentiation, rather than sorting (Le Cabec et al. 1996).

The classical granule subsets are Azurophil or primary granules (AG), secondary granules (SG) and gelatinase granules (GG). Neutrophils also contain exocytosable storage cell organelles, storage vesicles (SV), formed by endocytosis they contain many cell-surface markers and extracellular, plasma proteins (Borregaard et al. 1992). Ficolin-1-rich granules (FG) are like GGs highly exocytosable but gelatinase-poor (Rorvig et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
23650620	Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors Rørvig, S, Østergaard, O, Heegaard, NH, Borregaard, N	J. Leukoc. Biol.	2013
17627888	Neutrophil granules: a library of innate immunity proteins Borregaard, N, Sørensen, OE, Theilgaard-Mönch, K	Trends Immunol.	2007
1378856	Stimulus-dependent secretion of plasma proteins from human neutrophils Borregaard, N, Kjeldsen, L, Rygaard, K, Bastholm, L, Nielsen, MH, Sengeløv, H, Bjerrum, OW, Johnsen, AH	J. Clin. Invest.	1992
20338884	Neutrophil function in inflammation and inflammatory diseases Wright, HL, Moots, RJ, Bucknall, RC, Edwards, SW	Rheumatology (Oxford)	2010
8692836	Targeting of proteins to granule subsets is determined by timing and not by sorting: The specific granule protein NGAL is localized to azurophil granules when expressed in HL-60 cells Le Cabec, V, Cowland, JB, Calafat, J, Borregaard, N	Proc. Natl. Acad. Sci. U.S.A.	1996