The polymeric mucin Muc5ac is required for allergic airway hyperreactivity

Nature Communications

Volumn 6, Issue , 2015, Pages

  Evans, Christopher M ^a   Raclawska, Dorota S ^a   Ttofali, Fani ^a   Liptzin, Deborah R ^b   Fletcher, Ashley A ^a   Harper, Daniel N ^a   McGing, Maggie A ^a   McElwee, Melissa M ^c   Williams, Olatunji W ^d   Sanchez, Elizabeth ^c   Roy, Michelle G ^c   Kindrachuk, Kristen N ^e   Wynn, Thomas A ^e   Eltzschig, Holger K ^a   Blackburn, Michael R ^f   Tuvim, Michael J ^c   Janssen, William J ^a,g   Schwartz, David A ^a   Dickey, Burton F ^c  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b Nutrition Obesity Research Center at the University of Colorado   (United States)

^c UNIVERSITY OF TEXAS   (United States)

^d Peyton Manning Children's Hospital   (United States)

^e NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^f UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^g DEPARTMENT OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

METHACHOLINE; MUCIN 5AC; OVALBUMIN; ALLERGEN; METHACHOLINE CHLORIDE; MUC5AC PROTEIN, MOUSE;

AIRFLOW; ASTHMA; INHIBITION; MUSCLE; PATHOLOGY;

AIRWAY OBSTRUCTION; ALLERGIC AIRWAY HYPERREACTIVITY; ALLERGIC AIRWAY INFLAMMATION; ALLERGIC ASTHMA; ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASPERGILLUS ORYZAE; BAGG ALBINO MOUSE; BRONCHUS HYPERREACTIVITY; C57BL 6 MOUSE; CONTROLLED STUDY; EOSINOPHIL; FEMALE; IMMUNOHISTOCHEMISTRY; IMMUNOMODULATION; LEUKOCYTE; MALE; MOUSE; MUCUS SECRETION; NONHUMAN; POLYMERIZATION; PROTEIN EXPRESSION; WILD TYPE; ANIMAL; ASTHMA; C57BL MOUSE; CHEMISTRY; INFLAMMATION; LUNG; METABOLISM; MUCUS; SPECIES DIFFERENCE; TRANSGENIC MOUSE;

ASPERGILLUS; MUS;

ALLERGENS; ANIMALS; ASPERGILLUS ORYZAE; ASTHMA; BRONCHIAL HYPERREACTIVITY; FEMALE; IMMUNOHISTOCHEMISTRY; INFLAMMATION; LUNG; MALE; METHACHOLINE CHLORIDE; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; MICE, TRANSGENIC; MUCIN 5AC; MUCUS; OVALBUMIN; SPECIES SPECIFICITY;

EID: 84923361939     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms7281     Document Type: Article

References (67)

1. Fanta, C. H. Asthma. New Engl. J. Med. 360, 1002-1014 (2009).
2. Bosse, Y., Riesenfeld, E. P., Pare, P. D. & Irvin, C. G. It's not all smooth muscle: non-smooth-muscle elements in control of resistance to airflow. Annu. Rev. Physiol. 72, 437-462 (2010).
3. Wagers, S. S. et al. Extravascular fibrin, plasminogen activator, plasminogen activator inhibitors, and airway hyperresponsiveness. J. Clin. Invest. 114, 104-111 (2004).
4. Fahy, J. V. & Dickey, B. F. Airway mucus function and dysfunction. New Engl. J. Med. 363, 2233-2247 (2010).
5. Lundblad, L. K. et al. Airway hyperresponsiveness in allergically inflamed mice: the role of airway closure. Am. J. Respir. Crit. Care Med. 175, 768-774 (2007).
6. McCarthy, D. & Milic-Emili, J. Closing volume in asymptomatic asthma. Am. Rev. Respir. Dis. 107, 559-570 (1973).
7. Wagers, S. S. et al. Intrinsic and antigen-induced airway hyperresponsiveness are the result of diverse physiological mechanisms. J. Appl. Physiol. (1985) 102, 221-230 (2007).
8. Wagers, S., Lundblad, L. K., Ekman, M., Irvin, C. G. & Bates, J. H. The allergic mouse model of asthma: normal smooth muscle in an abnormal lung? J. Appl. Physiol. 96, 2019-2027 (2004).
9. Evans, C. M. et al. Mucin is produced by clara cells in the proximal airways of antigen-challenged mice. Am. J. Respir. Cell Mol. Biol. 31, 382-394 (2004).
10. Woodruff, P. G. et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am. J. Respir. Crit. Care Med. 180, 388-395 (2009).
11. Fahy, J. V. Goblet cell and mucin gene abnormalities in asthma. Chest 122, 320S-326S (2002).
12. Ordonez, C. L. et al. Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. Am. J. Respir. Crit. Care Med. 163, 517-523 (2001).
13. Takeyama, K., Fahy, J. V. & Nadel, J. A. Relationship of epidermal growth factor receptors to goblet cell production in human bronchi. Am. J. Respir. Crit. Care Med. 163, 511-516 (2001).
14. Zudhi Alimam, M. et al. Muc-5/5ac mucin messenger RNA and protein expression is a marker of goblet cell metaplasia in murine airways. Am. J. Respir. Cell Mol. Biol. 22, 253-260 (2000).
15. Kuyper, L. M. et al. Characterization of airway plugging in fatal asthma. Am. J. Med. 115, 6-11 (2003).
16. Aikawa, T., Shimura, S., Sasaki, H., Ebina, M. & Takishima, T. Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest 101, 916-921 (1992).
17. Dunnill, M. S. The pathology of asthma, with special reference to changes in the bronchial mucosa. J. Clin. Pathol. 13, 27-33 (1960).
18. The Collaborative Study on the Genetics of Asthma. A genome-wide search for asthma susceptibility loci in ethnically diverse populations. The Collaborative Study on the Genetics of Asthma (CSGA). Nat. Genet. 15, 389-392 (1997).
19. Sheehan, J. K., Richardson, P. S., Fung, D. C., Howard, M. & Thornton, D. J. Analysis of respiratory mucus glycoproteins in asthma: a detailed study from a patient who died in status asthmaticus. Am. J. Respir. Cell Mol. Biol. 13, 748-756 (1995).
20. Innes, A. L. et al. Ex vivo sputum analysis reveals impairment of proteasedependent mucus degradation by plasma proteins in acute asthma. Am. J. Respir. Crit. Care Med. 180, 203-210 (2009).
21. Singer, M. et al. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nat. Med. 10, 193-196 (2004).
22. Foster, W. M. et al. MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac. Am. J. Physiol. Lung Cell. Mol. Physiol. 299, L345-L352 (2010).
23. Kirkham, S., Sheehan, J. K., Knight, D., Richardson, P. S. & Thornton, D. J. Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B. Biochem. J. 361, 537-546 (2002).
24. Young, H. W. et al. Central role of Muc5ac expression in mucous metaplasia and its regulation by conserved 5' elements. Am. J. Respir. Cell Mol. Biol. 37, 273-290 (2007).
25. Roy, M. G. et al. Muc5b is required for airway defence. Nature 505, 412-416 (2014).
26. Koeppen, M. et al. Detrimental role of the airway mucin Muc5ac during ventilator-induced lung injury. Mucosal Immunol. 6, 762-775 (2013).
27. Busse, W. W. & Lemanske, Jr. R. F. Asthma. New Engl. J. Med. 344, 350-362 (2001).
28. Holt, P. G. & Sly, P. D. Th2 cytokines in the asthma late-phase response. Lancet 370, 1396-1398 (2007).
29. Corren, J. et al. Lebrikizumab treatment in adults with asthma. New Engl. J. Med. 365, 1088-1098 (2011).
30. Wills-Karp, M. et al. Interleukin-13: central mediator of allergic asthma. Science 282, 2258-2261 (1998).
31. Grunig, G. et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282, 2261-2263 (1998).
32. Hershey, G. K. IL-13 receptors and signaling pathways: an evolving web. J. Allergy Clin. Immunol. 111, 677-690 (2003).
33. Perkins, C. et al. Selective stimulation of IL-4 receptor on smooth muscle induces airway hyperresponsiveness in mice. J. Exp. Med. 208, 853-867 (2011).
34. Kuperman, D. A. et al. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat. Med. 8, 885-889 (2002).
35. Zhen, G. et al. IL-13 and epidermal growth factor receptor have critical but distinct roles in epithelial cell mucin production. Am. J. Respir. Cell Mol. Biol. 36, 244-253 (2007).
36. Takeyama, K. et al. Epidermal growth factor system regulates mucin production in airways. Proc. Natl Acad. Sci. USA 96, 3081-3086 (1999).
37. Hasnain, S. Z. et al. Muc5ac: a critical component mediating the rejection of enteric nematodes. J. Exp. Med. 208, 893-900 (2011).
38. Kheradmand, F. et al. A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease. J. Immunol. 169, 5904-5911 (2002).
39. Takeda, K., Haczku, A., Lee, J. J., Irvin, C. G. & Gelfand, E. W. Strain dependence of airway hyperresponsiveness reflects differences in eosinophil localization in the lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 281, L394-L402 (2001).
40. Kim, K. C. & Lee, B. C. P2 purinoceptor regulation of mucin release by airway goblet cells in primary culture. Br. J. Pharmacol. 103, 1053-1056 (1991).
41. Lethem, M. I. et al. Nucleotide regulation of goblet cells in human airway epithelial explants: normal exocytosis in cystic fibrosis. Am. J. Respir. Cell Mol. Biol. 9, 315-322 (1993).
42. Govindaraju, V., Martin, J. G., Maghni, K., Ferraro, P. & Michoud, M. C. The effects of extracellular purines and pyrimidines on human airway smooth muscle cells. J. Pharmacol. Exp. Ther. 315, 941-948 (2005).
43. Johansson, M. E. et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl Acad. Sci. USA 105, 15064-15069 (2008).
44. Lundgren, J. D. & Vestbo, J. The pathophysiological role of mucus production in inflammatory airway diseases. Respir. Med. 89, 315-316 (1995).
45. Israel, E. et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 364, 1505-1512.
46. Shan, M. et al. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 342, 447-453 (2013).
47. Hogg, J. C. The pathology of asthma. Clin. Chest Med. 5, 567-571 (1984).
48. O'Riordan, T. G., Zwang, J. & Smaldone, G. C. Mucociliary clearance in adult asthma. Am. Rev. Respir. Dis. 146, 598-603 (1992).
49. Innes, A. L. et al. The H antigen at epithelial surfaces is associated with susceptibility to asthma exacerbation. Am. J. Respir. Crit. Care Med. 183, 189-194 (2011).
50. Verdugo, P. Supramolecular dynamics of mucus. Cold Spring Harb. Perspect. Med. 2, a009597 (2012).
51. Daviskas, E. et al. Inhalation of hypertonic saline aerosol enhances mucociliary clearance in asthmatic and healthy subjects. Eur. Respir. J. 9, 725-732 (1996).
52. Falliers, C. J. & Cato, A. Controlled trial of bronchodilator-mucolytic aerosols, combined and separate. Ann. Allergy 40, 77-83 (1978).
53. Rao, S., Wilson, D. B., Brooks, R. C. & Sproule, B. J. Acute effects of nebulization of N-acetylcysteine on pulmonary mechanics and gas exchange. Am. Rev. Respir. Dis. 102, 17-22 (1970).
54. Tam, J., Nash, E. F., Ratjen, F., Tullis, E. & Stephenson, A. Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis. Cochrane Database Syst. Rev. 7, CD007168 (2013).
55. Gillissen, A. et al. Nacystelyn, a novel lysine salt of N-acetylcysteine, to augment cellular antioxidant defence in vitro. Respir. Med. 91, 159-168 (1997).
56. Suk, J. S. et al. N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles. Mol. Ther. 19, 1981-1989 (2011).
57. Jayaraman, S., Song, Y. & Verkman, A. S. Airway surface liquid pH in welldifferentiated airway epithelial cell cultures and mouse trachea. Am. J. Physiol. Cell Physiol. 281, C1504-C1511 (2001).
58. Alevy, Y. G. et al. IL-13-induced airway mucus production is attenuated by MAPK13 inhibition. J. Clin. Invest. 122, 4555-4568 (2012).
59. Woodruff, P. G. et al. Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 181, 438-445 (2010).
60. Tsao, P. N. et al. Notch signaling prevents mucous metaplasia in mouse conducting airways during postnatal development. Development 138, 3533- 3543 (2011).
61. Chen, G. et al. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. J. Clin. Invest. 119, 2914-2924 (2009).
62. Park, K. S. et al. SPDEF regulates goblet cell hyperplasia in the airway epithelium. J. Clin. Invest. 117, 978-988 (2007).
63. Schroeder, B. W. et al. AGR2 is induced in asthma and promotes allergeninduced mucin overproduction. Am. J. Respir. Cell Mol. Biol. 47, 178-185 (2012).
64. Foster, M. W., Yang, Z., Potts, E. N., Michael Foster, W. & Que, L. G. Snitrosoglutathione supplementation to ovalbumin-sensitized and -challenged mice ameliorates methacholine-induced bronchoconstriction. Am. J. Physiol. Lung Cell. Mol. Physiol. 301, L739-L744 (2011).
65. Piccotti, L., Dickey, B. F. & Evans, C. M. Assessment of intracellular mucin content in vivo. Methods Mol. Biol. 842, 279-295 (2012).
66. Roy, M. G. et al. Mucin production during prenatal and postnatal murine lung development. Am. J. Respir. Cell Mol. Biol. 44, 755-760 (2011).
67. Hsia, C. C., Hyde, D. M., Ochs, M. & Weibel, E. R. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am. J. Respir. Crit. Care Med. 181, 394-418 (2010).