Sialic Acid-Binding Lectins as Potential Pathophysiological Targets in Treatment of Chronic Bronchopulmonary Diseases (Review)

The article is devoted to the problem of finding the pathophysiological targets for optimizing the treatment of common and socially significant chronic respiratory diseases — bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). The balance between pro-inflammatory and anti-inflammatory mechanisms determines the nature of inflammation in these diseases. Among the regulators of inflammation there are siglecs — sialic acid-binding immunoglobulin-like lectins able to interact with terminal sialic acid present in all cells. Siglecs are involved in regulating cell proliferation, differentiation, apoptosis and implementing cell-cell interactions. The key role in modulating the regulatory activity of siglecs is in their ability to interact with ligands.

Although research on the structure and biological functions of siglecs in the body has only recently started, the prospects for this research are promising, especially with respect to BA and COPD treatment. Siglecs are mainly expressed by immune and peripheral blood cells. Pathophysiological mechanisms of BA and COPD are implemented with participation of eosinophils, mast cells, neutrophils, and macrophages. The siglecs expressed on them play a particular role in the severity of tissue damage caused by the influence of these cells and therefore can be attractive targets for treatment of chronic inflammatory diseases of the respiratory organs.

Siglec-8 and Siglec-10 molecules expressed on eosinophils have been actively studied in BA pathogenesis. However, given the importance of not only eosinophils, but also other cells in the disease pathogenesis, it seems challenging to investigate the role of Siglec-3, Siglec-5, Siglec-6, and Siglec-14 expressed on mast cells and basophils. In recent years, the role of Siglec-3, Siglec-9, and Siglec-5/14 has been studied in the pathogenesis of COPD. The use of antibodies against Siglec-15 described recently may be relevant in treatment of osteoporosis often associated with COPD.

Based on scientific literature data, this article reviews the role of siglecs as possible regulators of inflammation in patients with chronic bronchopulmonary diseases.

1. European Community Respiratory Health Survey. 2016. URL: http://www.ecrhs.org/.
2. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (GOLD). 2016. URL: http://www.ginasthma.com.
3. NICE. Asthma: diagnosis, monitoring and chronic asthma management. NICE Guideline. 2017. URL: https://www.nice.org.uk/guidance/ng80.
4. Кytikova O.Yu., Gvozdenko T.A. Functional relationships of homeostatic systems in pathological conditions. Uspekhi sovremennogo estestvoznaniya 2014; 5: 211–212.
5. Bogovin L.V., Kolosov V.P., Perel’man Yu.M. Nefarmakologicheskie sposoby dostizheniya kontrolya bronkhial’noy astmy [Non-pharmacological methods for manegement of bronchial asthma]. Vladivostok: Dal’nauka; 2016; 252 p.
6. Fu J., McDonald V., Gibson P., Simpson J. Systemic inflammation in older adults with asthma-COPD overlap syndrome. Allergy Asthma Immunol Res 2014; 6(4): 316–324, https://doi.org/10.4168/aair.2014.6.4.316.
7. Nakawah M., Hawkins C., Barbandi F. Asthma, chronic obstructive pulmonary disease (COPD), and the overlap syndrome. J Am Board Fam Med 2013; 26(4): 470–477, https://doi.org/10.3122/jabfm.2013.04.120256.
8. Lübbers J., Rodríguez E., van Kooyk Y. Modulation of immune tolerance via Siglec-sialic acid interactions. Front Immunol 2018; 9: 2807, https://doi.org/10.3389/fimmu.2018.02807.
9. Eakin A.J., Bustard M.J., McGeough C.M., Ahmed T., Bjourson A.J., Gibson D.S. Siglec-1 and -2 as potential biomarkers in autoimmune disease. Proteomics Clin Appl 2016; 10(6): 635–644, https://doi.org/10.1002/prca.201500069.
10. Lehmann F., Gäthje H., Kelm S., Dietz F. Evolution of sialic acid-binding proteins: molecular cloning and expression of fish siglec-4. Glycobiology 2014; 14(11): 959–968, https://doi.org/10.1093/glycob/cwh120.
11. Crocker P.R., McMillan S.J., Richards H.E. CD33-related siglecs as potential modulators of inflammatory responses. Ann N Y Acad Sci 2012; 1253: 102–111, https://doi.org/10.1111/j.1749-6632.2011.06449.x.
12. Pillai S., Netravali I.A., Cariappa A., Mattoo H. Siglecs and immune regulation. Annu Rev Immunol 2012; 30: 357–392, https://doi.org/10.1146/annurev-immunol-020711-075018.
13. Wang Y., Neumann H. Alleviation of neurotoxicity by microglial human Siglec-11. J Neurosci 2010; 30(9): 3482–3488, https://doi.org/10.1523/jneurosci.3940-09.2010.
14. Lopez P.H. Role of myelin-associated glycoprotein (Siglec-4a) in the nervous system. Adv Neurobiol 2014; 9: 245–262, https://doi.org/10.1007/978-1-4939-1154-7_11.
15. Delputte P.L., Van Gorp H., Favoreel H.W., Hoebeke I., Delrue I., Dewerchin H., Verdonck F., Verhasselt B., Cox E., Nauwynck H.J. Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages. PLoS One 2011; 6: e16827, https://doi.org/10.1371/journal.pone.0016827.
16. Chen W.C., Sigal D.S., Saven A., Paulson J.C. Targeting B lymphoma with nanoparticles bearing glycan ligands of CD22. Leuk Lymphoma 2012; 53(2): 208–210, https://doi.org/10.3109/10428194.2011.604755.
17. Álvarez B., Escalona Z., Uenishi H., Toki D., Revilla C., Yuste M., Del Moral M.G., Alonso F., Ezquerra A., Domínguez J. Molecular and functional characterization of porcine Siglec-3/CD33 and analysis of its expression in blood and tissues. Dev Comp Immunol 2015; 51(2): 238–250, https://doi.org/10.1016/j.dci.2015.04.002.
18. Nordström T., Movert E., Olin A.I., Ali S.R., Nizet V., Varki A., Areschoug T. Human Siglec-5 inhibitory receptor and immunoglobulin A (IgA) have separate binding sites in streptococcal beta protein. J Biol Chem 2011; 286(39): 33981–33991, https://doi.org/10.1074/jbc.m111.251728.
19. Varchetta S., Brunetta E., Roberto A., Mikulak J., Hudspeth K.L., Mondelli M.U., Mavilio D. Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes. PLoS One 2012; 7(9): e45821, https://doi.org/10.1371/journal.pone.0045821.
20. Gao P.S., Shimizu K., Grant A.V., Rafaels N., Zhou L.F., Hudson S.A., Konno S., Zimmermann N., Araujo M.I., Ponte E.V., Cruz A.A., Nishimura M., Su S.N., Hizawa N., Beaty T.H., Mathias R.A., Rothenberg M.E., Barnes K.C., Bochner B.S. Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma. Eur J Hum Genet 2010; 18(6): 713–719, https://doi.org/10.1038/ejhg.2009.239.
21. Retamal J., Sörensen J., Lubberink M., Suarez-Sipmann F., Borges J.B., Feinstein R., Jalkanen S., Antoni G., Hedenstierna G., Roivainen A., Larsson A., Velikyan I. Feasibility of (68)Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome. Am J Nucl Med Mol Imaging 2016; 6(1): 18–31.
22. Bandala-Sanchez E., Zhang Y., Reinwald S., Dromey J.A., Lee B.H., Qian J., Böhmer R.M., Harrison L.C. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat Immunol 2013; 14(7): 741–748, https://doi.org/10.1038/ni.2610.
23. Wang X., Mitra N., Cruz P., Deng L.; NISC Comparative Sequencing Program, Varki N., Angata T., Green E.D., Mullikin J., Hayakawa T., Varki A. Evolution of Siglec-11 and Siglec-16 genes in hominins. Mol Biol Evol 2012; 29(8): 2073–2086, https://doi.org/10.1093/molbev/mss077.
24. Ali S.R., Fong J.J., Carlin A.F., Busch T.D., Linden R., Angata T., Areschoug T., Parast M., Varki N., Murray J., Nizet V., Varki A. Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. J Exp Med 2014; 211(6): 1231–1242, https://doi.org/10.1084/jem.20131853.
25. Crocker P.R., Paulson J.C., Varki A. Siglecs and their roles in the immune system. Nat Rev Immunol 2007; 7(4): 255–266, https://doi.org/10.1038/nri2056.
26. Cao H., Lakner U., de Bono B., Traherne J.A., Trowsdale J., Barrow A.D. SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non-functional alleles in humans. Eur J Immunol 2008; 38(8): 2303–2315, https://doi.org/10.1002/eji.200738078.
27. Gunten S.V., Bochner B.S. Basic and clinical immunology of siglecs. Ann N Y Acad Sci 2008; 1143(1): 61–82, https://doi.org/10.1196/annals.1443.011.
28. Kawai T., Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11(5): 373–384, https://doi.org/10.1038/ni.1863.
29. Pisetsky D.S. The origin and properties of extracellular DNA: from PAMP to DAMP. Clin Immunol 2012; 144(1): 32–40, https://doi.org/10.1016/j.clim.2012.04.006.
30. Cao H., Crocker P.R. Evolution of CD33-related siglecs: regulating host immune functions and escaping pathogen exploitation? Immunology 2011; 132(1): 18–26, https://doi.org/10.1111/j.1365-2567.2010.03368.x.
31. Heung L.J., Hohl T.M. DAP12 inhibits pulmonary immune responses to cryptococcus neoformans. Infect Immun 2016; 84(6): 1879–1886, https://doi.org/10.1128/iai.00222-16.
32. Spahn J.H., Li W., Bribriesco A.C., Liu J., Shen H., Ibricevic A., Pan J.H., Zinselmeyer B.H., Brody S.L., Goldstein D.R., Krupnick A.S., Gelman A.E., Miller M.J., Kreisel D. DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation. J Immunol 2015; 194(8): 4039–4048, https://doi.org/10.4049/jimmunol.1401415.
33. Angata T., Nycholat C.M., Macauley M.S. Therapeutic targeting of Siglecs using antibody- and glycan-based approaches. Trends Pharmacol Sci 2015; 36(10): 645–660, https://doi.org/10.1016/j.tips.2015.06.008.
34. Nitschke L. Suppressing the antibody response with Siglec ligands. N Engl J Med 2013; 369(14): 1373–1374, https://doi.org/10.1056/NEJMcibr1308953.
35. Chang L., Chen Y.J., Fan C.Y., Tang C.J., Chen Y.H., Low P.Y., Ventura A., Lin C.C., Chen Y.J., Angata T. Identification of Siglec ligands using a proximity labeling method. J Proteome Res 2017; 16(10): 3929–3941, https://doi.org/10.1021/acs.jproteome.7b00625.
36. Bochner B.S. “Siglec”ting the allergic response for therapeutic targeting. Glycobiology 2017; 26(6): 546–552, https://doi.org/10.1093/glycob/cww024.
37. Pappas K., Papaioannou A.I., Kostikas K., Tzanakis N. The role of macrophages in obstructive airways disease: chronic obstructive pulmonary disease and asthma. Cytokine 2013; 64: 613–625, https://doi.org/10.1016/j.cyto.2013.09.010.
38. Bochner B.S., Book W., Busse W.W., Butterfield J., Furuta G.T., Gleich G.J., Klion A.D., Lee J.J., Leiferman K.M., Minnicozzi M., Moqbel R., Rothenberg M.E., Schwartz L.B., Simon H.U., Wechsler M.E., Weller P.F. Workshop report from the National Institutes of Health Taskforce on the Research Needs of Eosinophil-Associated Diseases (TREAD). J Allergy Clin Immunol 2012; 130(3): 587–596, https://doi.org/10.1016/j.jaci.2012.07.024.
39. Van Schayck O.C. Global strategies for reducing the burden from asthma. Prim Care Respir J 2013; 22(2): 239–243, https://doi.org/10.4104/pcrj.2013.00052.
40. Kolobovnikova Yu.V., Urazova O.I., Novitsky V.V., Litvinova L.S., Chumakova S.P. Eosinophil: a modern concept of the kinetics, structure, and function. Gematologiya i transfusiologiya 2012; 57(1): 30–36.
41. Kelly E.A., Esnault S., Johnson S.H., Liu L.Y., Malter J.S., Burnham M.E., Jarjour N.N. Human eosinophil activin A synthesis and mRNA stabilization are induced by the combination of IL-3 plus TNF. Immunol Cell Biol 2016; 94(7): 701–708, https://doi.org/10.1038/icb.2016.30.
42. Wilkerson E.M., Johansson M.W., Hebert A.S., Westphall M.S., Mathur S.K., Jarjour N.N., Schwantes E.A., Mosher D.F., Coon J.J. The peripheral blood eosinophil proteome. J Proteome Res 2016; 15: 1524–1533, https://doi.org/10.1021/acs.jproteome.6b00006.
43. Amin K., Janson C., Bystrom J. Role of eosinophil granulocytes in allergic airway inflammation endotypes. Scand J Immunol 2016; 84(2): 75–85, https://doi.org/10.1111/sji.12448.
44. Doyle A.D., Jacobsen E.A., Ochkur S.I., McGarry M.P., Shim K.G., Nguyen D.T., Protheroe C., Colbert D., Kloeber J., Neely J., Shim K.P., Dyer K.D., Rosenberg H.F., Lee J.J., Lee N.A. Expression of the secondary granule proteins major basic protein 1 (MBP-1) and eosinophil peroxidase (EPX) is required for eosinophilopoiesis in mice. Blood 2013; 122(5): 781–790, https://doi.org/10.1182/blood-2013-01-473405.
45. Furuta G.T., Nieuwenhuis E.E., Karhausen J., Gleich G., Blumberg R.S., Lee J.J., Ackerman S.J. Eosinophils alter colonic epithelial barrier function: role for major basic protein. Am J Physiol Gastrointest Liver Physiol 2005; 289(5): 890–897, https://doi.org/10.1152/ajpgi.00015.2005.
46. Kim C.-K. Eosinophil-derived neurotoxin: a novel biomarker for diagnosis and monitoring of asthma. Korean J Pediatr 2013; 56(1): 8–12, https://doi.org/10.3345/kjp.2013.56.1.8.
47. Tulic M.K., Sly P.D., Andrews D., Crook M., Davoine F., Odemuyiwa S.O., Charles A., Hodder M.L., Prescott S.L., Holt P.G., Moqbel R. Thymic indoleamine 2,3-dioxygenase-positive eosinophils in young children: potential role in maturation of the naive immune system. J Pathol 2009; 175(5): 2043–2052, https://doi.org/10.2353/ajpath.2009.090015.
48. Lee J.J., Jacobsen E.A., McGarry M.P., Schleimer R., Lee N.A. Eosinophils in health and disease: the LIAR hypothesis. Clin Exp Allergy 2010; 40(4): 563–575, https://doi.org/10.1111/j.1365-2222.2010.03484.x.
49. Wu D., Molofsky A.B., Liang H.E., Ricardo-Gonzalez R.R., Jouihan H.A., Bando J.K., Chawla A., Locksley R.M. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 2011; 332(6026): 243–247, https://doi.org/10.1126/science.1201475.
50. Bischoff L., Derk C.T. Eosinophilic fasciitis: demographics, disease pattern and response to treatment: report of 12 cases and review of the literature. Int J Dermatol 2008; 47(1): 29–35, https://doi.org/10.1111/j.1365-4632.2007.03544.x.
51. Straumann A., Aceves S.S., Blanchard C., Collins M.H., Furuta G.T., Hirano I., Schoepfer A.M., Simon D., Simon H.U. Pediatric and adult eosinophilic esophagitis: similarities and differences. Allergy 2012; 677(4): 477–490, https://doi.org/10.1111/j.1398-9995.2012.02787.x.
52. Jia Y., Yu H., Fernandes S.M., Wei Y., Gonzalez-Gil A., Motari M.G., Vajn K., Stevens W.W., Peters A.T., Bochner B.S., Kern R.C., Schleimer R.P., Schnaar R.L. Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells. J Allergy Clin Immunol 2015; 135(3): 799–810, https://doi.org/10.1016/j.jaci.2015.01.004.
53. Kiwamoto T., Kawasaki N., Paulson J.C., Bochner B.S. Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions. Pharmacol Ther 2012; 135(3): 327–336, https://doi.org/10.1016/j.pharmthera.2012.06.005.
54. Nutku E., Aizawa H., Hudson S.A., Bochner B.S. Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis. Blood 2003; 101(12): 5014–5020, https://doi.org/10.1182/blood-2002-10-3058.
55. Janevska D., O’Sullivan J., Cao Y., Bochner B.S. Specific subsets of kinases mediate Siglec-8 engagement-induced reactive oxygen species (ROS) production and apoptosis in primary human eosinophils. Glycobiology 2015; 25: 1214.
56. Tateno Н., Crocker P.R., Paulson J.C. Mouse Siglec-F and human Siglec-8 are functionally convergent paralogs that are selectively expressed on eosinophils and recognize 6′-sulfo-sialyl Lewis X as a preferred glycan ligand. Glycobiology 2005; 15(11): 1125–1135.
57. Suzukawa M., Miller M., Rosenthal P., Cho J.Y., Doherty T.A., Varki A., Broide D. Sialyltransferase ST3Gal-III regulates Siglec-F ligand formation and eosinophilic lung inflammation in mice. J Immunol 2013; 190(12): 5939–5948, https://doi.org/10.4049/jimmunol.1203455.
58. Li N., Zhang W., Wan T., Zhang J., Chen T., Yu Y., Wang J., Cao X. Cloning and characterization of Siglec-10, a novel sialic acid binding member of the Ig superfamily, from human dendritic cells. J Biol Chem 2001; 276(30): 28106–28112, https://doi.org/10.1074/jbc.m100467200.
59. Pfrengle F., Macauley M.S., Kawasaki N., Paulson J.C. Copresentation of antigen and ligands of Siglec-G induces B cell tolerance independent of CD22. J Immunol 2013; 191(4): 1724–1731, https://doi.org/10.4049/jimmunol.1300921.
60. Toubai T., Rossi C., Oravecz-Wilson K., Zajac C., Liu C., Braun T., Fujiwara H., Wu J., Sun Y., Brabbs S., Tamaki H., Magenau J., Zheng P., Liu Y., Reddy P. Siglec-G represses DAMP-mediated effects on T cells. JCI Insight 2017; 2(14): 92293, https://doi.org/10.1172/jci.insight.92293.
61. Macauley M.S., Crocer P.R., Paulson J.C. Siglec regulation of immune cell function in disease. Nat Rev Immunol 2014; 14(10): 653–666, https://doi.org/10.1038/nri3737.
62. Escalona Z., Álvarez B., Uenishi H., Toki D., Yuste M., Revilla C., del Moral M.G., Alonso F., Ezquerra A., Domínguez J. Molecular characterization of porcine Siglec-10 and analysis of its expression in blood and tissues. Dev Comp Immunol 2015; 48(1): 116–123, https://doi.org/10.1016/j.dci.2014.09.011.
63. Liu J., Pang Z., Wang G., Guan X., Fang K., Wang Z., Wang F. Advanced role of neutrophils in common respiratory diseases. J Immunol Res 2017; 6710278, https://doi.org/10.1155/2017/6710278.
64. Rosales C., Demaurex N., Lowell C.A., Uribe-Querol E. Neutrophils: their role in innate and adaptive immunity. J Immunol Res 2016; 2016: 1469780, https://doi.org/10.1155/2016/1469780.
65. Guilliams M., Bruhns P., Saeys Y., Hammad H., Lambrecht B.N. The function of Fcgamma receptors in dendritic cells and macrophages. Nat Rev Immunol 2014; 14(2): 94–108, https://doi.org/10.1038/nri3582.
66. Pham D.L., Ban G.Y., Kim S.H., Shin Y.S., Ye Y.M., Chwae Y.J., Park H.S. Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma. Clin Exp Allergy 2017; 47(1): 57–70, https://doi.org/10.1111/cea.12859.
67. Alam R., Good J., Rollins D., Verma M., Chu H., Pham T.H., Martin R.J. Airway and serum biochemical correlates of refractory neutrophilic asthma. J Allergy Clin Immunol 2017; 140(4): 1004–1014.e13, https://doi.org/10.1016/j.jaci.2016.12.963.
68. Hosoki K., Itazawa T., Boldogh I., Sur S. Neutrophil recruitment by allergens contribute to allergic sensitization and allergic inflammation. Curr Opin Allergy Clin Immunol 2016; 16(1): 45–50, https://doi.org/10.1097/aci.0000000000000231.
69. Freeman C.M., Curtis J.L. Lung dendritic cells: shaping immune responses throughout COPD progression. Am J Respir Cell Mol Biol2017; 56(2): 152–159, https://doi.org/10.1165/rcmb.2016-0272tr.
70. Walter R.B., Raden B.W., Zeng R., Hausermann P., Bernstein I.D., Cooper J.A. ITIM-dependent endocytosis of CD33-related Siglecs: role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2. J Leukoc Biol 2008; 83(1): 200–211, https://doi.org/10.1189/jlb.0607388.
71. Hernández-Caselles T., Martínez-Esparza M., Pérez-Oliva A.B., Quintanilla-Cecconi A.M., García-Alonso A., Alvarez-López D.M., García-Peñarrubia P. A study of CD33 (Siglec-3) antigen expression and function on activated human T and NK cells: two isoforms of CD33 are generated by alternative splicing. J Leukoc Biol 2006; 79(1): 46–58, https://doi.org/10.1189/jlb.0205096.
72. Walter R.B. The role of CD33 as therapeutic target in acute myeloid leukemia. Expert Opin Ther Targets 2014; 18(7): 715–718, https://doi.org/10.1517/14728222.2014.909413.
73. Siddiqui S., Schwarz F., Springer S., Khedri Z., Yu H., Deng L., Verhagen A., Naito-Matsui Y., Jiang W., Kim D., Zhou J., Ding B., Chen X., Varki N., Varki A. Studies on the detection, expression, glycosylation, dimerization, and ligand binding properties of mouse Siglec-E. J Biol Chem 2017; 292(3): 1029–1037, https://doi.org/10.1074/jbc.m116.738351.
74. Ahtinen H., Kulkova J., Lindholm L., Eerola E., Hakanen A.J., Moritz N., Söderström M., Saanijoki T., Jalkanen S., Roivainen A., Aro H.T. 68Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections. EJNMMI Res 2014; 4: 45, https://doi.org/10.1186/s13550-014-0045-3.
75. Jandus C., Boligan K.F., Chijioke O., Liu H., Dahlhaus M., Démoulins T., Schneider C., Wehrli M., Hunger R.E., Baerlocher G.M., Simon H.U., Romero P., Münz C., von Gunten S. Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. J Clin Invest 2014; 124(4): 1810–1820, https://doi.org/10.1172/jci65899.
76. Yu H., Gonzalez-Gil A., Wei Y., Fernandes S.M., Porell R.N., Vajn K., Paulson J.C., Nycholat C.M., Schnaar R.L. Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties. Glycobiology 2017; 27(7): 657–668, https://doi.org/10.1093/glycob/cwx026.
77. Zeng Z., Li M., Wang M., Wu X., Li Q., Ning Q., Zhao J., Xu Y., Xie J. Increased expression of Siglec-9 in chronic obstructive pulmonary disease. Sci Rep 2017; 7(1): 10116, https://doi.org/10.1038/s41598-017-09120-5.
78. McMillan S.J., Sharma R.S., McKenzie E.J., Richards H.E., Zhang J., Prescott A., Crocker P.R. Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b beta2-integrin-dependent signaling. Blood 2013; 121(11): 2084–2094, https://doi.org/10.1182/blood-2012-08-449983.
79. McMillan S.J., Sharma R.S., Richards H.E., Hegde V., Crocker P.R. Siglec-E promotes beta2-integrin-dependent NADPH oxidase activation to suppress neutrophil recruitment to the lung. J Biol Chem 2014; 289(29): 20370–20376, https://doi.org/10.1074/jbc.m114.574624.
80. Schwarz F., Landig C.S., Siddiqui S., Secundino I., Olson J., Varki N., Nizet V., Varki A. Paired Siglec receptors generate opposite inflammatory responses to a human-specific pathogen. EMBO J 2017; 36(6): 751–760, https://doi.org/10.15252/embj.201695581.
81. Tanida S., Akita K., Ishida A., Mori Y., Toda M., Inoue M., Ohta M., Yashiro M., Sawada T., Hirakawa K., Nakada H. Binding of the sialic acid-binding lectin, Siglec-9, to the membrane mucin, MUC1, induces recruitment of β-catenin and subsequent cell growth. J Biol Chem 2013; 288(44): 31842–31852, https://doi.org/10.1074/jbc.m113.471318.
82. Millares L., Martí S., Ardanuy C., Liñares J., Santos S., Dorca J., García-Nuñez M., Quero S., Monsó E. Specific IgA against Pseudomonas aeruginosa in severe COPD. Int J Chron Obstruct Pulmon Dis 2017; 12: 2807–2811, https://doi.org/10.2147/copd.s141701.
83. Fahy J.V., Dickey B.F. Airway mucus function and dysfunction. N Engl J Med 2010; 363(23): 2233–2247, https://doi.org/10.1056/nejmra0910061.
84. Caramori G., Casolari P., Di Gregorio C., Saetta M., Baraldo S., Boschetto P., Ito K., Fabbri L.M., Barnes P.J., Adcock I.M., Cavallesco G., Chung K.F., Papi A. MUC5AC expression is increased in bronchial submucosal glands of stable COPD patients. Histopathology 2009; 55 (3): 321–31, https://doi.org/10.1111/j.1365-2559.2009.03377.x.
85. Fischer B.M., Wong J.K., Kummarapurugu A.B., Voynow J.A. Neutrophil elastase increases expression of senescence biomarkers in normal human bronchial epithelial cells. Am J Respir Crit Care Med 2011; 183: A2434, https://doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a2434.
86. Ishikawa N., Hattori N., Tanaka S., Horimasu Y., Haruta Y., Yokoyama A., Kohno N., Kinnula V.L. Levels of surfactant proteins A and D and KL-6 are elevated in the induced sputum of chronic obstructive pulmonary disease patients: a sequential sputum analysis. Respiration 2011; 82(1): 10–18, https://doi.org/10.1159/000324539.
87. Fan H., Bobek L.A. Regulation of human MUC7 Mucin gene expression by cigarette smoke extract or cigarette smoke and Pseudomonas aeruginosa lipopolysaccharide in human airway epithelial cells and in MUC7 transgenic mice. Open Respir Med J 2010; 4: 63–70, https://doi.org/10.2174/18743064010040100063.
88. Bottoni P., Scatena R. The role of CA 125 as tumor marker: biochemical and clinical aspects. Adv Exp Med Biol 2015; 867: 229–244, https://doi.org/10.1007/978-94-017-7215-0_14.
89. Yilmaz M.B., Zorlu A., Dogan O.T., Karahan O., Tandogan I., Akkurt I. Role of CA-125 in identification of right ventricular failure in chronic obstructive pulmonary disease. Clin Cardiol 2011; 34(4): 244–248, https://doi.org/10.1002/clc.20868.
90. Belisle J.A., Horibata S., Jennifer G.A., Petrie S., Kapur A., André S., Gabius H.J., Rancourt C., Connor J., Paulson J.C., Patankar M.S. Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes. Mol Cancer 2010; 9(1): 118, https://doi.org/10.1186/1476-4598-9-118.
91. Angata T., Hayakawa T., Yamanaka M., Varki A., Nakamura M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. FASEB J 2006; 20(12): 1964–1973, https://doi.org/10.1096/fj.06-5800com.
92. Yamanaka M., Kato Y., Angata T., Narimatsu H. Deletion polymorphism of Siglec14 and its functional implications. Glycobiology 2009; 19(8): 841–846, https://doi.org/10.1093/glycob/cwp052.
93. Pillai S.G., Kong X., Edwards L.D., Cho M.H., Anderson W.H., Coxson H.O., Lomas D.A., Silverman E.K.; ECLIPSE and ICGN Investigators. Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010; 182(12): 1498–1505, https://doi.org/10.1164/rccm.201002-0151OC.
94. Wielgat P., Mroz R.M., Stasiak-Barmuta A., Szepiel P., Chyczewska E., Braszko J.J., Holownia A. Inhaled corticosteroids increase Siglec-5/14 expression in sputum cells of COPD patients. Adv Exp Med Biol 2015; 839: 1–5, https://doi.org/10.1007/5584_2014_51.
95. Ishii T., Angata T., Wan E.S., Cho M.H., Motegi T., Gao C., Ohtsubo K., Kitazume S., Gemma A., ParÉ P.D., Lomas D.A., Silverman E.K., Taniguchi N., Kida K. Influence of SIGLEC 9 polymorphisms on COPD phenotypes including exacerbation frequency. Respirology 2017; 22(4): 684–690, https://doi.org/10.1111/resp.12952.
96. Angata T., Ishii T., Motegi T., Oka R., Taylor R.E., Soto P.C., Chang Y.C., Secundino I., Gao C.X., Ohtsubo K., Kitazume S., Nizet V., Varki A., Gemma A., Kida K., Taniguchi N. Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell Mol Life Sci 2013; 70(17): 3199–3210, https://doi.org/10.1007/s00018-013-1311-7.
97. Stuible M., Moraitis A., Fortin A., Saragosa S., Kalbakji A., Filion M., Tremblay G.B. Mechanism and function of monoclonal antibodies targeting Siglec-15 for therapeutic inhibition of osteoclastic bone resorption. J Biol Chem 2014; 289(10): 6498–6512, https://doi.org/10.1074/jbc.m113.494542.
98. Kiwamoto T., Katoh T., Evans C.M., Janssen W.J., Brummet M.E., Hudson S.A., Zhu Z., Tiemeyer M., Bochner B.S. Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis. J Allergy Clin Immunol 2015; 135(5): 1329–1340, https://doi.org/10.1016/j.jaci.2014.10.027.
99. Hiruma Y., Hirai T., Tsuda E. Siglec-15, a member of the sialic acid-binding lectin, is a novel regulator for osteoclast differentiation. Biochem Biophys Res Commun 2011; 409(3): 424–429, https://doi.org/10.1016/j.bbrc.2011.05.015.
100. Mroz R.M., Holownia A., Wielgat P., Sitko A., Skopinski T., Braszko J.J. Siglec-8 in induced sputum of COPD patients. Adv Exp Med Biol 2013; 788: 19–23, https://doi.org/10.1007/978-94-007-6627-3_3.

Kytikova O.Yu., Gvozdenko T.A., Antonyuk M.V., Novgorodtseva T.P. Sialic Acid-Binding Lectins as Potential Pathophysiological Targets in Treatment of Chronic Bronchopulmonary Diseases (Review). Sovremennye tehnologii v medicine 2019; 11(4): 151, https://doi.org/10.17691/stm2019.11.4.18