Neutrophil azurophilic granule glycoproteins are distinctively decorated by atypical pauci- and phosphomannose glycans.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
26 08 2021
26 08 2021
Historique:
received:
19
11
2020
accepted:
12
08
2021
entrez:
27
8
2021
pubmed:
28
8
2021
medline:
15
12
2021
Statut:
epublish
Résumé
While neutrophils are critical first-responders of the immune system, they also cause tissue damage and act in a variety of autoimmune diseases. Many neutrophil proteins are N-glycosylated, a post-translational modification that may affect, among others, enzymatic activity, receptor interaction, and protein backbone accessibility. So far, a handful neutrophil proteins were reported to be decorated with atypical small glycans (paucimannose and smaller) and phosphomannosylated glycans. To elucidate the occurrence of these atypical glycoforms across the neutrophil proteome, we performed LC-MS/MS-based (glyco)proteomics of pooled neutrophils from healthy donors, obtaining site-specific N-glycan characterisation of >200 glycoproteins. We found that glycoproteins that are typically membrane-bound to be mostly decorated with high-mannose/complex N-glycans, while secreted proteins mainly harboured complex N-glycans. In contrast, proteins inferred to originate from azurophilic granules carried distinct and abundant paucimannosylation, asymmetric/hybrid glycans, and glycan phosphomannosylation. As these same proteins are often autoantigenic, uncovering their atypical glycosylation characteristics is an important step towards understanding autoimmune disease and improving treatment.
Identifiants
pubmed: 34446797
doi: 10.1038/s42003-021-02555-7
pii: 10.1038/s42003-021-02555-7
pmc: PMC8390755
doi:
Substances chimiques
Glycoproteins
0
Polysaccharides
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1012Informations de copyright
© 2021. The Author(s).
Références
Nathan, C. Neutrophils and immunity: challenges and opportunities. Nat. Rev. Immunol. 6, 173–182 (2006).
pubmed: 16498448
doi: 10.1038/nri1785
Lekstrom-Himes, J. A. & Gallin, J. I. Immunodeficiency diseases caused by defects in phagocytes. N. Engl. J. Med. 343, 1703–1714 (2000).
pubmed: 11106721
doi: 10.1056/NEJM200012073432307
Pillay, J. et al. In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood 116, 625–627 (2010).
pubmed: 20410504
doi: 10.1182/blood-2010-01-259028
Hickey, M. J. & Kubes, P. Intravascular immunity: the host–pathogen encounter in blood vessels. Nat. Rev. Immunol. 9, 364–375 (2009).
pubmed: 19390567
doi: 10.1038/nri2532
Rorvig, S., Ostergaard, O., Heegaard, N. H. & Borregaard, N. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors. J. Leukoc. Biol. 94, 711–721 (2013).
pubmed: 23650620
doi: 10.1189/jlb.1212619
Cieutat, A. M. et al. Azurophilic granules of human neutrophilic leukocytes are deficient in lysosome-associated membrane proteins but retain the mannose 6-phosphate recognition marker. Blood 91, 1044–1058 (1998).
pubmed: 9446668
doi: 10.1182/blood.V91.3.1044
Henson, P. M. & Johnston, R. B. Jr. Tissue injury in inflammation. Oxidants, proteinases, and cationic proteins. J. Clin. Investig. 79, 669–674 (1987).
pubmed: 3546374
pmcid: 424175
doi: 10.1172/JCI112869
Liu, J. et al. Advanced role of neutrophils in common respiratory diseases. J. Immunol. Res. 2017, 6710278 (2017).
pubmed: 28589151
pmcid: 5447318
doi: 10.1155/2017/6710278
Bossuyt, X. et al. Position paper: revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat. Rev. Rheumatol. 13, 683–692 (2017).
pubmed: 28905856
doi: 10.1038/nrrheum.2017.140
van der Geest, K. S. M. et al. Towards precision medicine in ANCA-associated vasculitis. Rheumatology 57, 1332–1339 (2018).
pubmed: 29045715
doi: 10.1093/rheumatology/kex367
Cornec, D., Cornec-Le Gall, E., Fervenza, F. C. & Specks, U. ANCA-associated vasculitis—clinical utility of using ANCA specificity to classify patients. Nat. Rev. Rheumatol. 12, 570–579 (2016).
pubmed: 27464484
doi: 10.1038/nrrheum.2016.123
Varki, A. et al. Essentials of Glycobiology, 3rd edn (Cold Spring Harbor Laboratory Press, Cold Spring Harbor (NY), 2015–2017).
Yu, J. T. et al. Deglycosylation of myeloperoxidase uncovers its novel antigenicity. Kidney Int. 91, 1410–1419 (2017).
pubmed: 28187981
doi: 10.1016/j.kint.2016.12.012
Falck, D. et al. Glycoforms of immunoglobulin G based biopharmaceuticals are differentially cleaved by trypsin due to the glycoform influence on higher-order structure. J. Proteome Res. 14, 4019–4028 (2015).
pubmed: 26244886
doi: 10.1021/acs.jproteome.5b00573
Specks, U. et al. Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies. J. Biochem. 141, 101–112 (2007).
pubmed: 17158864
doi: 10.1093/jb/mvm008
Babu, P. et al. Structural characterisation of neutrophil glycans by ultra sensitive mass spectrometric glycomics methodology. Glycoconj. J. 26, 975–986 (2009).
pubmed: 18587645
doi: 10.1007/s10719-008-9146-4
Venkatakrishnan, V. et al. Glycan analysis of human neutrophil granules implicates a maturation-dependent glycosylation machinery. J. Biol. Chem. 295, 12648–12660 (2020).
pubmed: 32665399
doi: 10.1074/jbc.RA120.014011
Loke, I., Ostergaard, O., Heegaard, N. H. H., Packer, N. H. & Thaysen-Andersen, M. Paucimannose-Rich N-glycosylation of spatiotemporally regulated human neutrophil elastase modulates its immune functions. Mol. Cell Proteom. 16, 1507–1527 (2017).
doi: 10.1074/mcp.M116.066746
Loke, I., Packer, N. H. & Thaysen-Andersen, M. Complementary LC–MS/MS-based N-glycan, N-glycopeptide, and intact N-glycoprotein profiling reveals unconventional Asn71-glycosylation of human neutrophil cathepsin G. Biomolecules 5, 1832–1854 (2015).
pubmed: 26274980
pmcid: 4598777
doi: 10.3390/biom5031832
Zoega, M., Ravnsborg, T., Hojrup, P., Houen, G. & Schou, C. Proteinase 3 carries small unusual carbohydrates and associates with alphalpha-defensins. J. Proteom. 75, 1472–1485 (2012).
doi: 10.1016/j.jprot.2011.11.019
Thaysen-Andersen, M. et al. Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. J. Biol. Chem. 290, 8789–8802 (2015).
pubmed: 25645918
pmcid: 4423670
doi: 10.1074/jbc.M114.631622
Ugonotti, J., Chatterjee, S. & Thaysen-Andersen, M. Structural and functional diversity of neutrophil glycosylation in innate immunity and related disorders. Mol. Asp. Med. https://doi.org/10.1016/j.mam.2020.100882 (2020).
doi: 10.1016/j.mam.2020.100882
Tjondro, H. C., Loke, I., Chatterjee, S. & Thaysen-Andersen, M. Human protein paucimannosylation: cues from the eukaryotic kingdoms. Biol. Rev. Camb. Philos. Soc. 94, 2068–2100 (2019).
pubmed: 31410980
doi: 10.1111/brv.12548
Reiding, K. R. et al. Neutrophil myeloperoxidase harbors distinct site-specific peculiarities in its glycosylation. J. Biol. Chem. 294, 20233–20245 (2019).
pubmed: 31719144
pmcid: 6937560
doi: 10.1074/jbc.RA119.011098
Tjondro, H. C. et al. Hyper-truncated Asn355- and Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase. J. Biol. Chem. 296, 100144 (2021).
pubmed: 33273015
doi: 10.1074/jbc.RA120.016342
Reiding, K. R., Bondt, A., Franc, V. & Heck, A. J. R. The benefits of hybrid fragmentation methods for glycoproteomics. Trac-Trend Anal. Chem. 108, 260–268 (2018).
doi: 10.1016/j.trac.2018.09.007
Caval, T. et al. Targeted analysis of lysosomal directed proteins and their sites of mannose-6-phosphate modification. Mol. Cell. Proteom. 18, 16–27 (2019).
doi: 10.1074/mcp.RA118.000967
Caval, T., Zhu, J. & Heck, A. J. R. Simply extending the mass range in electron transfer higher energy collisional dissociation increases confidence in N-glycopeptide identification. Anal. Chem. 91, 10401–10406 (2019).
pubmed: 31287300
pmcid: 6706795
doi: 10.1021/acs.analchem.9b02125
Grabowski, P. et al. Proteome analysis of human neutrophil granulocytes from patients with monogenic disease using data-independent acquisition. Mol. Cell. Proteom. 18, 760–772 (2019).
doi: 10.1074/mcp.RA118.001141
Rieckmann, J. C. et al. Social network architecture of human immune cells unveiled by quantitative proteomics. Nat. Immunol. 18, 583–593 (2017).
pubmed: 28263321
doi: 10.1038/ni.3693
Raijmakers, R., Heck, A. J. & Mohammed, S. Assessing biological variation and protein processing in primary human leukocytes by automated multiplex stable isotope labeling coupled to 2 dimensional peptide separation. Mol. Biosyst. 5, 992–1003 (2009).
pubmed: 19668865
doi: 10.1039/b901873e
Kistowski, M. et al. A strong neutrophil elastase proteolytic fingerprint marks the carcinoma tumor proteome. Mol. Cell Proteom. 16, 213–227 (2017).
doi: 10.1074/mcp.M116.058818
Bern, M., Kil, Y. J. & Becker, C. Byonic: advanced peptide and protein identification software. Curr. Protoc. Bioinform. Chapter 13, Unit 13, 20 (2012).
Nairn, A. V. et al. Regulation of glycan structures in animal tissues: transcript profiling of glycan-related genes. J. Biol. Chem. 283, 17298–17313 (2008).
pubmed: 18411279
pmcid: 2427342
doi: 10.1074/jbc.M801964200
Riley, N. M., Hebert, A. S., Westphall, M. S. & Coon, J. J. Capturing site-specific heterogeneity with large-scale N-glycoproteome analysis. Nat. Commun. 10, 1311 (2019).
pubmed: 30899004
pmcid: 6428843
doi: 10.1038/s41467-019-09222-w
Caval, T., Heck, A. J. R. & Reiding, K. R. Meta-heterogeneity: evaluating and describing the diversity in glycosylation between sites on the same glycoprotein. Mol. Cell. Proteom. https://doi.org/10.1074/mcp.R120.002093 (2020).
van Berkel, P. H., van Veen, H. A., Geerts, M. E., de Boer, H. A. & Nuijens, J. H. Heterogeneity in utilization of N-glycosylation sites Asn624 and Asn138 in human lactoferrin: a study with glycosylation-site mutants. Biochem. J. 319, 117–122 (1996).
pubmed: 8870657
pmcid: 1217743
doi: 10.1042/bj3190117
Zhu, J. et al. Quantitative longitudinal inventory of the N-glycoproteome of human milk from a single donor reveals the highly variable repertoire and dynamic site-specific changes. J. Proteome Res. https://doi.org/10.1021/acs.jproteome.9b00753 (2020).
Stadlmann, J. et al. Comparative glycoproteomics of stem cells identifies new players in ricin toxicity. Nature 549, 538–542, (2017).
pubmed: 28959962
pmcid: 6003595
doi: 10.1038/nature24015
Ruhaak, L. R., Xu, G., Li, Q., Goonatilleke, E. & Lebrilla, C. B. Mass spectrometry approaches to glycomic and glycoproteomic analyses. Chem. Rev. 118, 7886–7930 (2018).
pubmed: 29553244
pmcid: 7757723
doi: 10.1021/acs.chemrev.7b00732
Gaunitz, S., Nagy, G., Pohl, N. L. & Novotny, M. V. Recent advances in the analysis of complex glycoproteins. Anal. Chem. 89, 389–413 (2017).
pubmed: 28105826
doi: 10.1021/acs.analchem.6b04343
Lee, W. C. & Lee, K. H. Applications of affinity chromatography in proteomics. Anal. Biochem. 324, 1–10 (2004).
pubmed: 14654038
doi: 10.1016/j.ab.2003.08.031
Yang, Y. et al. Hybrid mass spectrometry approaches in glycoprotein analysis and their usage in scoring biosimilarity. Nat. Commun. 7, 13397 (2016).
pubmed: 27824045
pmcid: 5105167
doi: 10.1038/ncomms13397
Nakayama, F. et al. CD15 expression in mature granulocytes is determined by alpha 1,3-fucosyltransferase IX, but in promyelocytes and monocytes by alpha 1,3-fucosyltransferase IV. J. Biol. Chem. 276, 16100–16106 (2001).
pubmed: 11278338
doi: 10.1074/jbc.M007272200
Evrard, M. et al. Developmental analysis of bone marrow neutrophils reveals populations specialized in expansion, trafficking, and effector functions. Immunity 48, 364–379 e368 (2018).
pubmed: 29466759
doi: 10.1016/j.immuni.2018.02.002
Varki, A. Selectin ligands. Proc. Natl Acad. Sci. USA 91, 7390–7397 (1994).
pubmed: 7519775
pmcid: 44407
doi: 10.1073/pnas.91.16.7390
Graham, S. A. et al. Identification of neutrophil granule glycoproteins as Lewis(x)-containing ligands cleared by the scavenger receptor C-type lectin. J. Biol. Chem. 286, 24336–24349 (2011).
pubmed: 21561871
pmcid: 3129213
doi: 10.1074/jbc.M111.244772
Aplin, A. E., Howe, A., Alahari, S. K. & Juliano, R. L. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharm. Rev. 50, 197–263 (1998).
pubmed: 9647866
Clerc, F. et al. Human plasma protein N-glycosylation. Glycoconj. J. 33, 309–343 (2016).
pubmed: 26555091
doi: 10.1007/s10719-015-9626-2
Totten, S. M., Feasley, C. L., Bermudez, A. & Pitteri, S. J. Parallel comparison of N-linked glycopeptide enrichment techniques reveals extensive glycoproteomic analysis of plasma enabled by SAX-ERLIC. J. Proteome Res. 16, 1249–1260 (2017).
pubmed: 28199111
doi: 10.1021/acs.jproteome.6b00849
Kolarich, D., Weber, A., Turecek, P. L., Schwarz, H. P. & Altmann, F. Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge isoforms. Proteomics 6, 3369–3380 (2006).
pubmed: 16622833
doi: 10.1002/pmic.200500751
Varki, A. Biological roles of glycans. Glycobiology 27, 3–49 (2017).
pubmed: 27558841
doi: 10.1093/glycob/cww086
Dahms, N. M., Lobel, P. & Kornfeld, S. Mannose 6-phosphate receptors and lysosomal enzyme targeting. J. Biol. Chem. 264, 12115–12118 (1989).
pubmed: 2545698
doi: 10.1016/S0021-9258(18)63825-6
Ghosh, P., Dahms, N. M. & Kornfeld, S. Mannose 6-phosphate receptors: new twists in the tale. Nat. Rev. Mol. Cell Biol. 4, 202–212 (2003).
pubmed: 12612639
doi: 10.1038/nrm1050
Le Cabec, V., Cowland, J. B., Calafat, J. & Borregaard, N. 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. Proc. Natl Acad. Sci. USA 93, 6454–6457 (1996).
pubmed: 8692836
pmcid: 39044
doi: 10.1073/pnas.93.13.6454
Pohlmann, R. et al. Mannose 6-phosphate specific receptors: structure and function. Biochem. Soc. Trans. 17, 15–16 (1989).
pubmed: 2541033
doi: 10.1042/bst0170015
Varki, A. et al. Symbol nomenclature for graphical representations of glycans. Glycobiology 25, 1323–1324 (2015).
pubmed: 26543186
pmcid: 4643639
doi: 10.1093/glycob/cwv091
Ceroni, A. et al. GlycoWorkbench: a tool for the computer-assisted annotation of mass spectra of glycans. J. Proteome Res. 7, 1650–1659 (2008).
pubmed: 18311910
doi: 10.1021/pr7008252
Kirschner, K. N. et al. GLYCAM06: a generalizable biomolecular force field. Carbohydr. J. Comput. Chem. 29, 622–655 (2008).
doi: 10.1002/jcc.20820