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Surfactant Protein D: A Therapeutic Target for Allergic Airway Diseases

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The Collectin Protein Family and Its Multiple Biological Activities

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Abstract

Surfactant protein D (SP-D), expressed in respiratory epithelium, is important for modulating both innate and adaptive immunity against inhaled allergens. This chapter evaluates the key immunomodulatory role of SP-D in allergic airway inflammatory events. Studies have shown that SP-D ameliorated various cellular mechanisms implicated in pulmonary allergic reactions, including allergic eosinophilia through induction of apoptosis and clearance of activated eosinophils, and inhibition of basophils activation. In addition, blocking allergen-specific IgE synthesis, T cell proliferation, and hindrance to the binding of allergen-IgE complex to B lymphocytes are also brought about by SP-D. In vitro, a recombinant fragment of human SP-D, composed of homotrimeric neck and C-type lectin domains (rfhSP-D), binds to allergens derived from Aspergillus fumigatus, house dust mite and grass pollen in a calcium-dependent manner and inhibits specific IgE interaction with allergens. Murine models of hypersensitivity reactions, when treated with rfhSP-D, showed reduced levels of IgE, clearance of peripheral and pulmonary eosinophilia, and Th2 polarisation to Th1 type. SP-D knock-out mice accordingly show hypereosinophilia and predominantly exaggerated Th2 response following allergen challenge; these features can be ameliorated by rfhSP-D treatment. The current state of the filed appears to suggest that rfhSP-D is an excellent therapeutic immunomodulator in airway allergic diseases.

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References

  • Acharya KR, Ackerman SJ. Eosinophil granule proteins: form and function. J Biol Chem. 2014;289:17406–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Allinne J, Scott G, Lim WK, Birchard D, Erjefält JS, Sandén C, Ben L-H, Agrawal A, Kaur N, Kim JH. IL-33 blockade affects mediators of persistence and exacerbation in a model of chronic airway inflammation. J Allergy Clin Immunol. 2019;144:1624–37. e10

    Article  CAS  PubMed  Google Scholar 

  • Borron PJ, Crouch EC, Lewis JF, Wright JR, Possmayer F, Fraher LJ. Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production. J Immunol. 1998;161:4599–603.

    Article  CAS  PubMed  Google Scholar 

  • Breiteneder H, Diamant Z, Eiwegger T, Fokkens WJ, Traidl-Hoffmann C, Nadeau K, O’hehir RE, O’mahony L, Pfaar O, Torres MJ. Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care. Allergy. 2019;74:2293–311.

    Article  PubMed  Google Scholar 

  • Brinker KG, Martin E, Borron P, Mostaghel E, Doyle C, Harding CV, Wright JR. Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells. Am J Phys Lung Cell Mol Phys. 2001;281:L1453–63.

    CAS  Google Scholar 

  • Carreto-Binaghi LE, Taylor ML. Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response. Respir Res. 2016;17:1–7.

    Article  CAS  Google Scholar 

  • Cheng G, Ueda T, Numao T, Kuroki Y, Nakajima H, Fukushima Y, Motojima S, Fukuda T. Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma. Eur Respir J. 2000;16:831–5.

    Article  CAS  PubMed  Google Scholar 

  • Conrad DH, Ford JW, Sturgill JL, Gibb DR. CD23: an overlooked regulator of allergic disease. Curr Allergy Asthma Rep. 2007;7:331–7.

    Article  CAS  PubMed  Google Scholar 

  • Corrigan C, Haczku A, Gemou-Engesaeth V, Doi S, Kikuchi Y, Takatsu K, Durham S, Kay A. CD4 T-lymphocyte activation in asthma is accompanied by increased serum concentrations of interleukin-5: effect of glucocorticoid therapy. Am Rev Respir Dis. 1993;147:540–7.

    Article  CAS  PubMed  Google Scholar 

  • Crawford A, Macleod M, Schumacher T, Corlett L, Gray D. Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol. 2006;176:3498–506.

    Article  CAS  PubMed  Google Scholar 

  • Crouch E, Parghi D, Kuan S, Persson A. Surfactant protein D: subcellular localization in nonciliated bronchiolar epithelial cells. Am J Phys Lung Cell Mol Phys. 1992;263:L60–6.

    CAS  Google Scholar 

  • De Vooght V, Carlier V, Devos FC, Haenen S, Verbeken E, Nemery B, Hoet PH, Vanoirbeek JA. B-lymphocytes as key players in chemical-induced asthma. PLoS One. 2013;8:e83228.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Desch AN, Henson PM, Jakubzick CV. Pulmonary dendritic cell development and antigen acquisition. Immunol Res. 2013;55:178–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drake LY, Iijima K, Hara K, Kobayashi T, Kephart GM, Kita H. B cells play key roles in th2-type airway immune responses in mice exposed to natural airborne allergens. PLoS One. 2015;10:e0121660.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Erpenbeck V, Ziegert M, Cavalet-Blanco D, Martin C, Baelder R, Glaab T, Braun A, Steinhilber W, Luettig B, Uhlig S. Surfactant protein D inhibits early airway response in Aspergillus fumigatus-sensitized mice. Clin Exp Allergy. 2006;36:930–40.

    Article  CAS  PubMed  Google Scholar 

  • Esnault S, Kelly EA. Essential mechanisms of differential activation of eosinophils by IL-3 compared to GM-CSF and IL-5. Crit Rev Immunol. 2016;36(5):429–44.

    PubMed  PubMed Central  Google Scholar 

  • Felton JM, Lucas CD, Rossi AG, Dransfield I. Eosinophils in the lung–modulating apoptosis and efferocytosis in airway inflammation. Front Immunol. 2014;5:302.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fisher JH, Larson J, Cool C, Dow SW. Lymphocyte activation in the lungs of SP-D null mice. Am J Respir Cell Mol Biol. 2002;27:24–33.

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388:2128–41.

    Article  CAS  PubMed  Google Scholar 

  • Ghosh S, Hoselton SA, Schuh JM. μ-chain–deficient mice possess B-1 cells and produce IgG and IgE, but not IgA, following systemic sensitization and inhalational challenge in a fungal asthma model. J Immunol. 2012;189:1322–9.

    Article  CAS  PubMed  Google Scholar 

  • Haczku A. Protective role of the lung collectins surfactant protein A and surfactant protein D in airway inflammation. J Allergy Clin Immunol. 2008;122:861–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • HÃ¥kansson K, Lim NK, Hoppe H-J, Reid KB. Crystal structure of the trimeric α-helical coiled-coil and the three lectin domains of human lung surfactant protein D. Structure. 1999;7:255–64.

    Article  PubMed  Google Scholar 

  • Hamelmann E, Takeda K, Haczku A, Cieslewicz G, Shultz L, Hamid Q, **ng Z, Gauldie J, Gelfand EW. Interleukin (IL)-5 but Not Immunoglobulin E Reconstitutes Airway Inflammation and Airway Hyperresponsiveness in IL-4–Deficient Mice. Am J Respir Cell Mol Biol. 2000;23:327–34.

    Article  CAS  PubMed  Google Scholar 

  • Hansen S, Lo B, Evans K, Neophytou P, Holmskov U, Wright JR. Surfactant protein D augments bacterial association but attenuates major histocompatibility complex class II presentation of bacterial antigens. Am J Respir Cell Mol Biol. 2007;36:94–102.

    Article  CAS  PubMed  Google Scholar 

  • Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM, Johnson LL, Swain SL, Lund FE. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol. 2000;1:475–82.

    Article  CAS  PubMed  Google Scholar 

  • Hartl D, Griese M. Surfactant protein D in human lung diseases. Eur J Clin Investig. 2006;36:423–35.

    Article  CAS  Google Scholar 

  • Hellings PW, Fokkens WJ, Bachert C, Akdis CA, Bieber T, Agache I, Bernal-Sprekelsen M, Canonica GW, Gevaert P, Joos G. Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis–A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement. Allergy. 2017;72:1297–305.

    Article  CAS  PubMed  Google Scholar 

  • Holmskov U, Malhotra R, Sim RB, Jensenius JC. Collectins: collagenous C-type lectins of the innate immune defense system. Immunol Today. 1994;15:67–74.

    Article  CAS  PubMed  Google Scholar 

  • Hortobágyi L, Kierstein S, Krytska K, Zhu X, Das AM, Poulain F, Haczku A. Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice. J Allergy Clin Immunol. 2008;122:521–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jeffery PK, Haahtela T. Allergic rhinitis and asthma: inflammation in a one-airway condition. BMC Pulmon Med. 2006;6:S5.

    Article  Google Scholar 

  • Kishore U, Wang J-Y, Hoppe H-J, Reid KB. The α-helical neck region of human lung surfactant protein D is essential for the binding of the carbohydrate recognition domains to lipopolysaccharides and phospholipids. Biochem J. 1996;318:505–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kishore U, Greenhough TJ, Waters P, Shrive AK, Ghai R, Kamran MF, Bernal AL, Reid KB, Madan T, Chakraborty T. Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol Immunol. 2006;43:1293–315.

    Article  CAS  PubMed  Google Scholar 

  • Koopmans J, Van Der Zee J, Krop E, Lopuhaä C, Jansen H, Batenburg J. Serum surfactant protein D is elevated in allergic patients. Clin Exp Allergy. 2004;34:1827–33.

    Article  CAS  PubMed  Google Scholar 

  • Kratzer B, Pickl WF. Years in review: recent progress in cellular allergology. Int Arch Allergy Immunol. 2016;169:1–12.

    Article  CAS  PubMed  Google Scholar 

  • Kuruvilla ME, Lee FE-H, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56:219–33.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin K-W, Jen KY, Suarez CJ, Crouch EC, Perkins DL, Finn PW. Surfactant protein D-mediated decrease of allergen-induced inflammation is dependent upon CTLA4. J Immunol. 2010;184:6343–9.

    Article  CAS  PubMed  Google Scholar 

  • Lindell DM, Berlin AA, Schaller MA, Lukacs NW. B cell antigen presentation promotes Th2 responses and immunopathology during chronic allergic lung disease. PLoS One. 2008;3:e3129.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Linton P-J, Bautista B, Biederman E, Bradley ES, Harbertson J, Kondrack RM, Padrick RC, Bradley LM. Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo. J Exp Med. 2003;197:875–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu CF, Chen YL, Shieh CC, Yu CK, Reid K, Wang JY. Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice. Clin Exp Allergy. 2005;35:515–21.

    Article  CAS  PubMed  Google Scholar 

  • Macaubas C, Dekruyff RH, Umetsu DT. Respiratory tolerance in the protection against asthma. Curr Drug Target Inflammat Allergy. 2003;2:175–86.

    Article  CAS  Google Scholar 

  • Madan T, Kishore U, Shah A, Eggleton P, Strong P, Wang J-Y, Aggrawal S, Sarma P, Reid K. Lung surfactant proteins A and D can inhibit specific IgE binding to the allergens of Aspergillus fumigatus and block allergen-induced histamine release from human basophils. Clin Exp Immunol. 1997;110:241–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madan T, Kishore U, Singh M, Strong P, Clark H, Hussain EM, Reid KB, Sarma PU. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest. 2001;107:467–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahajan L, Madan T, Kamal N, Singh VK, Sim RB, Telang SD, Ramchand CN, Waters P, Kishore U, Sarma PU. Recombinant surfactant protein-D selectively increases apoptosis in eosinophils of allergic asthmatics and enhances uptake of apoptotic eosinophils by macrophages. Int Immunol. 2008;20:993–1007.

    Article  CAS  PubMed  Google Scholar 

  • Malhotra R, Thiel S, Reid K, Sim R. Human leukocyte C1q receptor binds other soluble proteins with collagen domains. J Exp Med. 1990;172:955–9.

    Article  CAS  PubMed  Google Scholar 

  • Malhotra R, Haurum J, Thiel S, Sim RB. Interaction of C1q receptor with lung surfactant protein A. Eur J Immunol. 1992;22:1437–45.

    Article  CAS  PubMed  Google Scholar 

  • Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol. 1994;12:991–1045.

    Article  CAS  PubMed  Google Scholar 

  • Méndez-Enríquez E, Hallgren J. Mast cells and their progenitors in allergic asthma. Front Immunol. 2019;10:821.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moser M, Murphy KM. Dendritic cell regulation of Th 1-Th 2 development. Nat Immunol. 2000;1:199–205.

    Article  CAS  PubMed  Google Scholar 

  • Novak N, Allam JP, Betten H, Haberstok J, Bieber T. The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies. Allergy. 2004;59:5–14.

    Article  CAS  PubMed  Google Scholar 

  • Ooi EH, Wormald PJ, Carney AS, James CL, Tan LW. Surfactant protein d expression in chronic rhinosinusitis patients and immune responses in vitro to Aspergillus and alternaria in a nasal explant model. Laryngoscope. 2007;117:51–7.

    Article  CAS  PubMed  Google Scholar 

  • Palm NW, Rosenstein RK, Medzhitov R. Allergic host defences. Nature. 2012;484:465–72.

    Article  CAS  PubMed  Google Scholar 

  • Pawankar R. Allergic diseases and asthma: a global public health concern and a call to action. World Allergy Organ J. 2014;7(1):12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Persson A, Chang D, Rust K, Moxley M, Longmore W, Crouch E. Purification and biochemical characterization of CP4 (SP-D), a collagenous surfactant-associated protein. Biochemistry. 1989;28:6361–7.

    Article  CAS  PubMed  Google Scholar 

  • Polverino E, Dimakou K, Hurst J, Martinez-Garcia M-A, Miravitlles M, Paggiaro P, Shteinberg M, Aliberti S, Chalmers JD. The overlap between bronchiectasis and chronic airway diseases: state of the art and future directions. Eur Respir J. 2018;2018:52.

    Google Scholar 

  • Possmayer F. Pulmonary perspective. Am Rev Respir Dis. 1988;138:990.

    Article  CAS  PubMed  Google Scholar 

  • Qaseem AS, Singh I, Pathan AA, Layhadi JA, Parkin R, Alexandra F, Durham SR, Kishore U, Shamji MH. A recombinant fragment of human surfactant protein D suppresses basophil activation and T-helper type 2 and B-cell responses in grass pollen–induced allergic inflammation. Am J Respir Crit Care Med. 2017;196:1526–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaub B, Westlake R, He H, Arestides R, Haley K, Campo M, Velasco G, Bellou A, Hawgood S, Poulain FR. Surfactant protein D deficiency influences allergic immune responses. Clin Exp Allergy. 2004;34:1819–26.

    Article  CAS  PubMed  Google Scholar 

  • Schleh C, Rothen-Rutishauser BM, Blank F, Lauenstein HD, Nassimi M, Krug N, Braun A, Erpenbeck VJ, Gehr P, Hohlfeld JM. Surfactant Protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model. Respir Res. 2012;13:1–10.

    Article  CAS  Google Scholar 

  • Singh M, Madan T, Waters P, Parida SK, Sarma PU, Kishore U. Protective effects of a recombinant fragment of human surfactant protein D in a murine model of pulmonary hypersensitivity induced by dust mite allergens. Immunol Lett. 2003;86:299–307.

    Article  CAS  PubMed  Google Scholar 

  • Sorensen GL. Surfactant protein D in respiratory and non-respiratory diseases. Front Med. 2018;5:18.

    Article  Google Scholar 

  • Staubach P, Metz M, Chapman-Rothe N, Sieder C, Bräutigam M, Maurer M, Weller K. Omalizumab rapidly improves angioedema-related quality of life in adult patients with chronic spontaneous urticaria: X-ACT study data. Allergy. 2018;73:576–84.

    Article  CAS  PubMed  Google Scholar 

  • Takeda K, Miyahara N, Rha Y-H, Taube C, Yang E-S, Joetham A, Kodama T, Balhorn AM, Dakhama A, Duez C. Surfactant protein D regulates airway function and allergic inflammation through modulation of macrophage function. Am J Respir Crit Care Med. 2003;168:783–9.

    Article  PubMed  Google Scholar 

  • Trischler J, Lieb A, Arnold M, Schulze J, Rosewich M, Schubert R, Bottoli I, Zielen S. Omalizumab effectively protects against early and late allergic responses in asthma after 4 weeks. Allergy. 2017;72:1912–5.

    Article  CAS  PubMed  Google Scholar 

  • Vass G, Scanlon S, Beers M, Haczku A. Surfactant protein (SP)-D suppresses antigenic and mitogenic T cell activation in vitro. J Allergy Clin Immunol. 2004;113:S252.

    Article  Google Scholar 

  • Von Bredow C, Hartl D, Schmid K, Schabaz F, Brack E, Reinhardt D, Griese M. Surfactant protein D regulates chemotaxis and degranulation of human eosinophils. Clin Exp Allergy. 2006;36:1566–74.

    Article  Google Scholar 

  • Voskamp A, Kormelink TG, Van Wijk RG, Hiemstra P, Taube C, De Jong E, Smits HH. Modulating local airway immune responses to treat allergic asthma: lessons from experimental models and human studies. Semin Immunopathol. 2020;2020:1–16.

    Google Scholar 

  • Wang J-Y, Reid KB. The immunoregulatory roles of lung surfactant collectins SP-A, and SP-D, in allergen-induced airway inflammation. Immunobiology. 2007;212:417–25.

    Article  CAS  PubMed  Google Scholar 

  • Wang J-Y, Kishore U, Lim B-L, Strong P, Reid KB. Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens. Clin Exp Immunol. 1996;106:367–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J-Y, Shieh C-C, You P-F, Lei H-Y, Reid KB. Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma. Am J Respir Crit Care Med. 1998;158:510–8.

    Article  CAS  PubMed  Google Scholar 

  • Winkler C, Hohlfeld JM. Surfactant and allergic airway inflammation. Swiss Med Wkly. 2013;143:w13818.

    PubMed  Google Scholar 

  • Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005;5:58–68.

    Article  CAS  PubMed  Google Scholar 

  • Yousefi S, Sharma SK, Stojkov D, Germic N, Aeschlimann S, Ge MQ, Flayer CH, Larson ED, Redai IG, Zhang S. Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation. J Leukoc Biol. 2018;104:205–14.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, London, UK

    Iesha Singh & Mohamed H. Shamji

  2. Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK

    Iesha Singh & Mohamed H. Shamji

  3. Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UK

    Nazar Beirag & Uday Kishore

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  1. Iesha Singh
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  2. Nazar Beirag
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  3. Uday Kishore
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  4. Mohamed H. Shamji
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Correspondence to Mohamed H. Shamji .

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Editors and Affiliations

  1. Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UK

    Uday Kishore

  2. Department of Innate Immunity, National Institute Research Reproductive Health, Mumbai, India

    Taruna Madan

  3. Department of Biochemistry, University of Oxford, Oxford, UK

    Robert B. Sim

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Singh, I., Beirag, N., Kishore, U., Shamji, M.H. (2021). Surfactant Protein D: A Therapeutic Target for Allergic Airway Diseases. In: Kishore, U., Madan, T., Sim, R.B. (eds) The Collectin Protein Family and Its Multiple Biological Activities. Springer, Cham. https://doi.org/10.1007/978-3-030-67048-1_6

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