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Airway mucus: its components and function

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Abstract

The airway surface liquid (ASL), often referred to as mucus, is a thin layer of fluid covering the luminal surface of the airway. The major function of mucus is to protect the lung through mucociliary clearance against foreign particles and chemicals entering the lung. The mucus is comprised of water, ions, and various kinds of macromolecules some of which possess the protective functions such as anti-microbial, anti-protease, and anti-oxidant activity. Mucus glycoproteins or mucins are mainly responsible for the viscoelastic property of mucus, which is crucial for the effective mucociliary clearance. There are at least eight mucin genes identified in the human airways, which will potentially generate various kinds of mucin molecules. At present, neither the exact structures of mucin proteins nor their regulation are understood although it seems likely that different types of mucins are involved in different functions and might also be associated with certain airway diseases. The fact that mucins are tightly associated with various macromolecules present in ASL seems to suggest that the defensive role of ASL is determined not only by these individual components but rather by a combination of these components. Collectively, mucins in ASL may be compared to aircraft carriers carrying various types of weapons in defense of airborne enemies.

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References

  • An, G., Luo, G., Wu, R., Expression of MUC2 gene is down-regulated by vitamin A at the transcriptional leve.in vitro in tracheobronchial epithelial cells.Am. J, Respir Cell Mol. Biol., 10, 546–551 (1994).

    CAS  Google Scholar 

  • Baraniuk, J. N., Shizari, T., Sabol, M., Ali, M., Underhill, C. B., Hyaluronan is exocytosed from serous, but not mucous cells, of human nasal and tracheobronchial submucosal glands.J Investig. Med., 44, 47–52 (1996).

    PubMed  CAS  Google Scholar 

  • Baruch, A., Hartmann, M. L., Yoeli, M., Adereth, Y., Greenstein, S., Stadler, Y., Skornik, Y., Zaretsky, J., Smorodinsky, N. I., Keydar, I., Wreschner, D. H., The breast cancer-associated MUC1 gene generates both a receptor and its cognate binding protein.Cancer Res., 59, 1552–1561 (1999).

    PubMed  CAS  Google Scholar 

  • Bernacki, S. H., Nelson, A. L., Abdullah, L., Sheehan, J. K., Harris, A., William-Davis, C., Randell, S. H., Mucin gene expression during differentiation of human airway epithelia in vitro. MUC4 and MUC5b are strongly induced.Am. J. Respir Cell Mol. Biol., 20, 595–604 (1999).

    PubMed  CAS  Google Scholar 

  • Bhaskar, K. R., O’Sullivan, D. D., Seltzer, J., Rossing, T. H., Drazen, J. M., Reid, L. M., Density gradient study of bronchial mucus aspirates from healthy volunteers (smokers and nonsmokers) and from patients with tracheostomy.Exp. Lung Res., 9, 289–308 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Bhaskar, K. R., O’Sullivan, D. D., Opaskar-Hincman, H., Reid, L. M., Coles, S. J., Density gradient analysis of secretions produced in vitro by human and canine airway mucosa: identification of lipids and proteoglycans in such secretions.Exp. Lung Res., 10, 401–422 (1986).

    Article  PubMed  CAS  Google Scholar 

  • Bhaskar, K. R., O’Sullivan, D. D., Opaskar-Hincman, H., Reid, L. M., Lipids in airway secretions.Eur. J. Respir. Dis. (Suppl), 153, 215–221 (1987).

    CAS  Google Scholar 

  • Boman, H. G., Peptide antibiotics and their role in innate immunity.Annu. Rev. Immunol., 13, 61–92 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Braga, V. M. M., Pemberton, L. F., Duhig, T., Gendler, S. J., Spatial and temporal expression of an epithelial mucin, Mud, during mouse development.Development, 115, 427–437 (1992).

    PubMed  CAS  Google Scholar 

  • Breuer, R., Christensen, T. G., Niles, R. M., Stone, P. J., Snider, G. L., Human neutrophil elastase causes glycoconjugate release from the epithelial cell surface of hamster trachea in organ culture.Am. Rev. Respir. Dis., 139, 779–782 (1989).

    PubMed  CAS  Google Scholar 

  • Buisine, M. P., Devisme, L., Copin, M. C., Durand-Reville, M., Gosselin, B., Aubert, J. P., Porchet, N., Developmental mucin gene expression in the human respiratory tract.Am. J. Respir. Cell Mol. Biol., 20, 209–218 (1999).

    PubMed  CAS  Google Scholar 

  • Carraway, K. L., Price-Schiavi, S. A., Komatsu, M., Idris, N., Perez, A., Li, P., Jepson, S., Zhu, X., Carvajal, M. E., Carraway, C. A., Multiple facets of sialomucin complex/ MUC4, a membrane mucin and ErbB2 ligand, in tumors and tissues (Y2K update).Front Biosci., 5, D95-D107 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Chen, Y., Zhao, Y. H., Wu, R., In silico cloning of mouse Muc5b gene and upregulation of its expression in mouse asthma model.Am. J. Respir. Crit. Care Med., 164, 1059–1066 (2001).

    PubMed  CAS  Google Scholar 

  • Christensen, T. G., Blanchard, G. C., Nolley, G., Hayes, J. A., Ultrastructural localization of endogenous peroxidase in the lower respiratory tract of the guinea pig.Cell Tissue Res., 214, 407–415 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Copin, M. C., Devisme, L., Buisine, M. P., Marquette, C. H., Wurtz, A., Aubert, J. P., Gosselin, B., Porchet, N., From normal respiratory mucosa to epidermoid carcinoma: expression of human mucin genes.Int. J. Cancer, 86, 162–168 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Dabbagh, K., Takeyama, K., Lee, H. M., Ueki, I. F., Lausier, J. A., Nadel, J. A., IL-4 induces mucin gene expression and goblet cell metaplasi.in vitro andin vivo.J. Immunol., 162, 6233–6237 (1999).

    PubMed  CAS  Google Scholar 

  • Desseyn, J. L., Aubert, J. P., Van Seuningen, I., Porchet, N., Laine, A., Genomic organization of the 3′ region of the human mucin gene MUC5B.J. Biol. Chem., 272, 16873–16883 (1997).

    Article  PubMed  CAS  Google Scholar 

  • De Water, R., Willems, L. N., Van Muijen, G. N., Franken, C., Fransen, J. A., Dijkman, J. H., Kramps, J. A., Ultrastructural localization of bronchial antileukoprotease in central and peripheral human airways by a gold-labeling technique using monoclonal antibodies.Am. Rev. Respir. Dis., 133, 882–890 (1986).

    PubMed  Google Scholar 

  • Dohrman, A., Tsuda, T., Escudier, E., Cardone, M., Jany, B., Gum, J., Kim, Y., Basbaum, C., Distribution of lysozyme and mucin (MUC2 and MUC3) mRNA in human bronchus.Exp. Lung Res., 20, 367–380 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Dohrman, A., Miyata, S., Gallup, M., Li, J. D., Chapelin, C., Coste, A., Escudier, E., Nadel, J., Basbaum, C., Mucin gene (MUC2 and MUC5AC) upregulation by Gram-positive and Gram-negative bacteria.Biochim. Biophys. Acta., 1406, 251–259 (1998).

    PubMed  CAS  Google Scholar 

  • Dufosse, J., Porchet, N., Audie, J. P., Guyonnet-Duperat, V., Laine, A., Van Seuningen, I., Marrakchi, S., Degand, P., Aubert, J. P., Degenerate 87-base pair tandem repeats create hydrophilic/hydrophobic alternating domains in human mucin peptides mapped to 11p15.Biochem. J., 293, 329–337 (1993).

    PubMed  CAS  Google Scholar 

  • Ellison, R. T., Boose, D., LaForce, F. M., Isolation of an antibacterial peptide from human lung lavage fluid.J. Infect. Dis., 151, 1123–1129 (1985).

    PubMed  CAS  Google Scholar 

  • Elrod, K. C., Moore, W. R., Abraham, W. M., Tanaka, R. D., Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep.Am. J. Respir. Crit. Care Med., 156, 375–381 (1997).

    PubMed  CAS  Google Scholar 

  • Forteza, R., Lieb, T., Aoki, T., Savani, R. C., Conner, G. E., Salathe, M., Hyaluronan serves a novel role in airway mucosal host defense.FASEB J., 15, 2179–2186 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Gendler, S. J., Lancaster, C. A., Taylor-Papadimitriou, J., Duhig, T., Peat, N., Burchell, J., Pemberton, L., Lalani, E. N., Wilson, D., Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin.J. Biol. Chem., 265, 15286–15293 (1990).

    PubMed  CAS  Google Scholar 

  • Gendler, S. J., Spicer, A. P., Epithelial mucin genes.Annu. Rev. Physiol., 57, 607–634 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Gerson, C., Sabater, J., Scuri, M., Torbati, A., Coffey, R., Abraham, J. W., Lauredo, I., Forteza, R., Wanner, A., Salathe, M., Abraham, W. M., Conner, G. E., The lactoperoxidase system functions in bacterial clearance of airways.Am. J. Respir. Cell Mol. Biol., 22, 665–671 (2000).

    PubMed  CAS  Google Scholar 

  • Gray, T. E., Guzman, K., Davis, C. W., Abdullah, L. H., Nettesheim, P., Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells.Am. J. Respir. Cell Mol. Biol., 14, 104–112 (1996).

    PubMed  CAS  Google Scholar 

  • Gray, T., Koo, J. S., Nettesheim, P., Regulation of mucous differentiation and mucin gene expression in the tracheobronchial epithelium.Toxicology, 160, 35–46 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Grutter, M. G., Fendrich, G., Huber, R., Bode, W., The 2.5 A X-ray crystal structure of the acid-stable proteinase inhibitor from human mucous secretions analyzed in its complex with bovine alpha-chymotrypsin.EMBO J., 7, 345–351 (1988).

    PubMed  CAS  Google Scholar 

  • Gum, J. R., Hicks, J. W., Toribara, N. W., Siddiki, B., Kim, Y. S., Molecular cloning of human intestinal mucin (MUC2) cDNA.J. Biol. Chem., 269, 2440–2446 (1994).

    PubMed  CAS  Google Scholar 

  • Guyonnet-Duperat, V., Audie, J. P., Debailleul, V., Laine, A., Buisine, M. P., Galiegue-Zouitina, S., Pigny, P., Degand, P., Aubert, J. P., Porchet, N., Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain for 11p15 mucin genes.Biochem. J., 305, 211–219 (1995).

    PubMed  Google Scholar 

  • Guzman, K., Gray, T E., Yoon, J. H., Nettesheim, P., Quantitation of mucin RNA by PCR reveals induction of both MUC2 and MUC5AC mRNA levels by retinoids.Am. J. Physiol. (Lung Cell Mol Physiol), 271, L1023-L1028 (1996).

    CAS  Google Scholar 

  • Hayashi, T., Takahashi, T., Motoya, S., Ishida, T., Itoh, F., Adachi, M., Hinoda, Y., Imai, K., MUC1 mucin core protein binds to the domain 1 of ICAM-1.Digestion, 63, 87–92 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Hilkens, J., Ligtenberg, M. J. L., Vos, H. L., Litvinov, S. V., Cell membrane-associated mucins and their adhesion-modulating property.Trends Biochem. Sci., 17, 359–363 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Holgate, S. T., Epithelial damage and response.Clin. Exp. Allergy, 30, 37–41 (2000).

    Article  PubMed  Google Scholar 

  • Houdret, N., Perini, J. M., Galabert, C., Scharfman, A., Humbert, P., Lamblin, G., Roussel, P., The high lipid content of respiratory mucins in cystic fibrosis is related to infection.Biochim. Biophys. Acta, 880, 54–61 (1986).

    PubMed  CAS  Google Scholar 

  • Huang, J., Olivenstein, R., Taha, R., Hamid, Q., Ludwig, M., Enhanced proteoglycan deposition in the airway wall of atopic asthmatics.Am. J. Respir. Crit. Care Med., 160, 725–729 (1999).

    PubMed  CAS  Google Scholar 

  • Jacquot, J., Hayem, A., Galabert, C., Functions of proteins and lipids in airway secretions.Eur. Respir. J., 5, 343–358 (1992).

    PubMed  CAS  Google Scholar 

  • Kai, H., Yoshitake, K., Hisatsune, A., Kido, T., Isohama, Y., Takahama, K., Miyata, T., Dexamethasone suppresses mucus production and MUC-2 and MUC-5AC gene expression by NCI-H292 cells.Am. J. Physiol., 271, L484-L488 (1996).

    PubMed  CAS  Google Scholar 

  • Karlsson, N. G., Johansson, M. E., Asker, N., Karlsson, H., Gendler, S. J., Carlstedt, I., Hansson, G. C., Molecular characterization of the large heavily glycosylated domain glycopeptide from the rat small intestinal Muc2 mucin.Glycoconj. J., 13, 823–831 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Kim, K. C., Possible requirement of collagen gel substratum for production of mucin-like glycoproteins by primary rabbit tracheal epithelial cells in culture.In Vitro, 21, 617–621 (1985).

    CAS  Google Scholar 

  • Kim, K. C., Wasano, K., Niles, R. M., Schuster, J. E., Stone, P. J., Brody, J. S., Human neutrophil elastase releases cell surface mucins from primary cultures of hamster tracheal epithelial cells.Proc. Natl. Acad. Sci. USA, 84, 9304–08 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Kim, K. C., Hincman, H. O., Bhaskar, K. R., Secretions from primary hamster tracheal epithelial cells in culture-. Mucin-like glycoproteins, proteoglycans and lipids.Exp. Lung Res., 15, 299–314 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Kim, K. C., Singh, B. N., Hydrophobicity of mucin-like glycoproteins secreted by cultured tracheal epithelial cells: Association with lipids.Exp. Lung Res., 16, 279–292 (1990a).

    Article  PubMed  CAS  Google Scholar 

  • Kim, K. C., Singh, B. N., Association of lipids with mucins may take place prior to secretion: Studies with primary tracheal epithelial cells in culture.Biorheology, 27, 491–501 (1990b).

    PubMed  CAS  Google Scholar 

  • Kim, K. C., Mucin-like glycoproteins secreted from cultured hamster tracheal surface epithelial cells: Their hydrophobic nature and amino acid composition.Exp. Lung Res., 17, 65–76 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Kim, K. C., Regulation of airway goblet cell mucin secretion. In, Airway Secretion: Physiological Bases for the Control of Mucus Hypersecretion. Takishima T and Shimura S (eds). Lung Biology in Health and Disease, Vol. 72, Marcel Dekker, New York, NY, pp. 433–449, (1994).

    Google Scholar 

  • Kim, K. C., Hyun, S. W., Kim, B. T., Meerzaman, D., Lee, M. K., Lillehoj, E. P., Pseudomonas adhesion to MUC1 mucins: A potential role of MUC1 mucins in clearance of inhaled bacteria. In, Cilia, Mucus and Mucociliary Interactions. Salathe, M (ed). Marcel Dekker, New York, NY, pp. 217–224, (2001).

    Google Scholar 

  • Kim, Y. D., Kwon, E. J., Kwon, T. K., Baek, S. H., Song, S. Y., Suh, J. S., Regulation of IL-1β-mediated MUC2 gene in NCI-H292 human airway epithelial cells.Biochem. Biophys. Res. Commun., 274, 112–116 (2000).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Konstan, M. W., Walenga, R. W., Hilliard, K. A., Hilliard, J. B., Leukotriene B4 markedly elevated in the epithelial lining fluid of patients with cystic fibrosis.Am. Rev. Respir. Dis., 148, 896–901 (1993).

    PubMed  CAS  Google Scholar 

  • LaForce, F. M., Boose, D. S., Effect of zinc and phosphate on an antibacterial peptide isolated from lung lavage.Infect. Immun, 45, 692–696 (1984).

    PubMed  CAS  Google Scholar 

  • Lan, M. S., Batra, S. K., Qi, W. N., Metzgar, R. S., Hollingsworth, M. A., Cloning and sequencing of a human pancreatic tumor mucin cDNA.J. Biol. Chem., 265, 15294–15299 (1990).

    PubMed  CAS  Google Scholar 

  • Li, J. D., Dohrman, A. F., Gallup, M., Miyata, S., Gum, J. R., Kim, Y. S., Nadel, J. A., Prince, A., Basbaum, C. B., Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease.Proc. Natl. Acad. Sci. USA, 94, 967–72 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Li, Y., Bharti, A., Chen, D., Gong, J., Kufe, D., Interaction of glycogen synthase kinase 3β with the DF3/MUC1 carcinoma-associated antigen and β-catenin.Mol. Cell Biol., 18, 7216–7224 (1998).

    PubMed  CAS  Google Scholar 

  • Li, Y., Kuwahara, H., Ren, J., Wen, G., Kufe, D., The c-Srctyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3β and p-catenin.J. Biol. Chem., 276, 6061–6064 (2001a).

    Article  PubMed  CAS  Google Scholar 

  • Li, Y., Martin, L. D., Minnicozzi, M., Greenfeder, S., Fine, J., Pettersen, C. A., Chorley, B., Adler, K. B., Enhanced expression of mucin genes in a guinea pig model of allergic asthma.Am. J. Respir. Cell Mol. Biol., 25, 644–651 (2001b).

    PubMed  CAS  Google Scholar 

  • Ligtenberg, M. J. L., Vos, H. L., Gennissen, A. M., Hilkens, J., Episialin, a carcinoma-associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini.J. Biol. Chem., 265, 5573–5578 (1990).

    PubMed  CAS  Google Scholar 

  • Ligtenberg, M. J. L., Kruijshaar, L., Buijs, F., van Meijer, M., Litvinov, S. V., Hilkens, J., Cell-associated episialin is a complex containing two proteins derived from a common precursor.J. Biol. Chem., 267, 6171–6177 (1992).

    PubMed  CAS  Google Scholar 

  • Lillehoj, E. P., Hyun, S. W., Kim, B. T., Zhang, X. G., Lee, D. I., Rowland, S., Kim, K. C., Mud mucins on the cell surface are adhesion sites for Pseudomonas aeruginosa.Am. J. Physiol. (Lung Cell Mol Physiol), 280, L181-L187 (2001).

    CAS  Google Scholar 

  • Lillehoj, E. P., Kim, B. T., Kim, K. C., Identification of Pseudomonas aeruginosa flagellin as an adhesin for Muc1 mucin.Am. J. Physiol. (Lung Cell Mol Physiol), 282, L751-L756 (2002).

    CAS  Google Scholar 

  • Longphre, M., Li, D., Gallup, M., Drori, E., Ordonez, C. L., Redman, T., Wenzel, S., Bice, D. E., Fahy, J. V., Basbaum, C., Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells.J. Clin. Invest., 104, 1375–1382 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Ferrer, A., Curull, V., Barranco, C., Garrido, M., Lloreta, J., Real, F X., de Bolos, C., Mucins as differentiation markers in bronchial epithelium. Squamous cell carcinoma and adenocarcinoma display similar expression patterns.Am. J. Respir. Cell Mol. Biol., 24, 22–29 (2001).

    PubMed  CAS  Google Scholar 

  • Louahed, J., Toda, M., Jen, J., Hamid, Q., Renauld, J. C., Levitt, R. C., Nicolaides, N. C., Interleukin-9 upregulates mucus expression in the airways.Am. J. Respir. Cell Mol. Biol., 22, 649–656 (2000).

    PubMed  CAS  Google Scholar 

  • Lukacs, N. W., Strieter, R. M., Chensue, S. W., Kunkel, S. L., Activation and regulation of chemokines in allergic airway inflammation.J. Leukoc. Biol., 59, 13–17 (1996).

    PubMed  CAS  Google Scholar 

  • Lundgren, J. D., Rieves, R. D., Mullol, J., Logun, C., Shelhamer, J. H., The effect of neutrophil protenase enzymes on the release of mucus from feline and human airway cultures.Respir. Med., 88, 511–518 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Meezaman, D., Charles, P., Daskal, E., Polymeropoulos, M. H., Martin, B. M., Rose, M. C., Cloning and analysis of cDNA encoding a major airway glycoprotein, human tracheobronchial mucin (MUC5).J. Biol. Chem., 269, 12932–12939 (1994).

    PubMed  CAS  Google Scholar 

  • Meerzaman, D., Xing, P. X., Kim, K. C., Construction and characterization of a chimeric receptor containing the cytoplasmic domain of MUC1 mucin.Am. J. Physiol. (Lung Cell Mol Physiol), 278, L625-L629 (2000).

    CAS  Google Scholar 

  • Moniaux, N., Escande, F., Porchet, N., Aubert, J. P., Batra, S. K., Structural organization and classification of the human mucin genes.Front. Biosci., 6, D1192-D1206 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Nadziejko, C. E., Slomiany, B. L., Slomiany, A., Most of the lipid in purulent sputum is bound to mucus glycoprotein.Exp. Lung Res., 19, 671–684 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Nadziejko, C., Finkelstein, Inhibition of neutrophil elastase by mucus glycoprotein.Am. J. Respir. Cell Mol. Biol., 11, 103–107 (1994).

    PubMed  CAS  Google Scholar 

  • Nakamura, H., Yoshimura, K., McElvaney, N. G., Crystal, R. G., Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line.J. Clin. Invest, 89, 1478–1484 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Noah, T. L., Blach, R., Cheng, P. W., Wood, R. E., Leigh, M. W., Nasal and bronchoalveolar lavage fluid cytokines in early cystic fibrosis.J. Infect. Dis., 175, 638–647 (1997).

    PubMed  CAS  Google Scholar 

  • Ohkawara, Y., Tamura, G., Iwasaki, T., Tanaka, A., Kikuchi, T., Shirato, K., Activation and transforming growth factor-beta production in eosinophils by hyaluronan.Am. J. Respir. Cell Mol. Biol., 23, 444–451 (2000).

    PubMed  CAS  Google Scholar 

  • O’Riordan, T. G., Otero, R., Mao, Y., Lauredo, I., Abraham, W. M., Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways.Am. J. Respir. Crit. Care Med., 155, 1522–1528 (1997).

    PubMed  CAS  Google Scholar 

  • Pandey, P., Kharbanda, S., Kufe, D., Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein.Cancer Res., 55, 4000–4003 (1995).

    PubMed  CAS  Google Scholar 

  • Park, H. R., Hyun, S. W., Kim, K. C., Expression of MUC1 mucin gene by hamster tracheal surface epithelial cells in primary culture.Am. J. Respir. Cell Mol. Biol., 15, 237–244 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Paul, E., Lee, D. I., Hyun, S. W., Gendler, S. J., Kim, K. C., Identification and characterization of high molecular-mass mucin-like glycoproteins in the plasma membrane of airway epithelial cells.Am. J. Respir. Cell Mol. Biol., 19, 681–690 (1998).

    PubMed  CAS  Google Scholar 

  • Paul, A., Picard, J., Mergey, M., Veissiere, D., Finkbeiner, W. E., Basbaum, C. B., Glycoconjugates secreted by bovine tracheal serous cells in culture.Arch. Biochem. Biophys., 260, 75–84 (1988).

    Article  PubMed  CAS  Google Scholar 

  • Perlmutter, D. H., Pierce, J. A., The alpha 1-antitrypsin gene and emphysema.Am. J. Physiol., 257, L147-L162 (1989).

    PubMed  CAS  Google Scholar 

  • Pigny, P., Guyonnet-Duperat, V., Hill, A. S., Pratt, W. S., Galiegue-Zouitina, S. D., ’Hooge, M. C., Laine, A., Van Seuningen, I., Degand, P., Gum, J. R., Kim, Y. S., Swallow, D. M., Aubert, J. P., Porchet, N., Human mucin genes assigned to 11p15.5: Identification and organization of a cluster of genes.Genomics, 38, 340–352 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Quinn, R. J., McGuckin, M. A., Phosphorylation of the cytoplasmic domain of the MUC1 mucin correlates with changes in cell-cell adhesion.Int. J. Cancer, 87, 499–506 (2000).

    Article  Google Scholar 

  • Renauld, J. C., New insights into the role of cytokines in asthma.J. Clin. Pathol., 54, 577–589 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Roca-Ferrer, J., Mullol, J., Xaubet, A., Benitez, P., Bernal-Sprekelsen, M., Shelhamer, J., Picado, C., Proinflammatory cytokines and eosinophil cationic protein on glandular secretion from human nasal mucosa: regulation by corticosteroids.J. Allergy Clin. Immunol., 108, 87–93 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Rose, M. C., Piazza, F. M., Chen, Y. A., Ailmam, M. Z., Bautista, M. V., Letwin, N., Rajput, B., Model systems for investigating mucin gene expression in airway diseases.J. Aerosol Med., 13, 245–261 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Sala, A., Murphy, R. C., Voelkel, N. F., Direct airway injury results in elevated levels of sulfidopeptide leukotrienes, detectable in airway secretions.Prostaglandins, 42, 1–7 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Salathe, M., Guldimann, P., Conner, G. E., Wanner, A., Hydrogen peroxide-scavenging properties of sheep airway mucus.Am. J. Respir. Crit. Care Med., 151, 1543–1550 (1995).

    PubMed  CAS  Google Scholar 

  • Salathe, M., Holdeby, M., Forteza, R., Abraham, W. M., Wanner, A., Conner, G. E., Isolation and characterization of a peroxidase from the airway.Am. J. Respir. Cell Mol. Biol., 17, 97–105 (1997).

    PubMed  CAS  Google Scholar 

  • Sallenave, J. M., Silva, A., Marsden, M. E., Ryle, A. P., Secretion of mucus proteinase inhibitor and elafin by Clara cell and type II pneumocyte cell lines.Am. J. Respir. Cell Mol. Biol., 8, 126–33 (1993).

    PubMed  CAS  Google Scholar 

  • Shankar, V., Gilmore, M. S., Elkins, R. C., Sachdev, G. P., A novel human airway mucin cDNA encodes a protein with unique tandem-repeat organization.Biochem. J., 300, 295–298 (1994).

    PubMed  CAS  Google Scholar 

  • Sharma, P., Dudus, L., Nielsen, P. A., Clausen, H., Yankaskas, J. R., Hollingsworth, M. A., Engelhardt, J. F., MUC5B and MUC7 are differentially expressed in mucous and serous cells of submucosal glands in human bronchial airways.Am. J. Respir. Cell Mol. Biol., 19, 30–37 (1998).

    PubMed  CAS  Google Scholar 

  • Sims, D. E., Home, M. M., Heterogeneity of the composition and thickness of tracheal mucus in rats.Am. J. Physiol., 273, L1036-L1041 (1997).

    PubMed  CAS  Google Scholar 

  • Singh, P. K., Jia, H. P., Wiles, K., Hesselberth, J., Liu, L., Conway, B. A., Greenberg, E. P., Valore, E. V., Welsh, M. J., Ganz, T., Tack, B. F., McCray, P. B. Jr., Production of beta-defensins by human airway epithelia.Proc. Natl. Acad. Sci. USA, 95, 14961–14966 (1998)

    Article  PubMed  CAS  Google Scholar 

  • Singh, P. K., Tack, B. F., McCray, P. B. Jr, Welsh, M. J., Synergistic and additive killing by antimicrobial factors found in human airway surface liquid.Am. J. Physiol. Lung Cell Mol. Physiol., 279, L799-L805 (2000).

    PubMed  CAS  Google Scholar 

  • Smith, J., Travis, J. S. M., Greenberg, E. P., Welsh, M. J., Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface liquid.Cell, 85, 229–236 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Snider, G. L., Lucey, E. C., Christensen, T. G., Stone, P. J., Calore, J. D., Catanese, A., Franzblau, C., Emphysema and bronchial secretory cell metaplasia induced in hamsters by human neutrophil products.Am. Rev. Respir. Dis., 129, 155–60 (1984).

    PubMed  CAS  Google Scholar 

  • Sommerhoff, C. P., Caughey, G. H., Finkbeiner, W. E., Lazarus, S. C., Basbaum, C. B., Nadel, J. A., Mast cell chymase. A potent secretagogue for airway gland serous cells.J. Immunol., 142, 2450–2456 (1989).

    PubMed  CAS  Google Scholar 

  • Sommerhoff, C. P., Nadel, J. A., Basbaum, C. B., Caughey, G. H., Neutrophil elastase and cathepsin G stimulate secretion from cultured bovine airway gland serous cells.J. Clin. Invest, 85, 682–689 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Taipale, J., Lohi, J., Saarinen, J., Kovanen, P. T., Keski-Oja, J., Human mast cell chymase and leukocyte elastase release latent transforming growth factor-beta 1 from the extracellular matrix of cultured human epithelial and endothelial cells.J. Biol. Chem., 270, 4689–4696 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Thompson, A. B., Bohling, T., Payvandi, F., Rennard, S. I., Lower respiratory tract lactoferrin and lysozyme arise primarily in the airways and are elevated in association with chronic bronchitis.J. Lab. Clin. Med., 115, 148–158 (1990).

    PubMed  CAS  Google Scholar 

  • Thompson, R. C., Ohlsson, K., Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase.Proc. Natl. Acad. Sci. USA, 83, 6692–6696 (1986).

    Article  PubMed  CAS  Google Scholar 

  • van de Bovenkamp, J. H., Hau, C. M., Strous, G. J., Buller, H. A., Dekker, J., Einerhand, A. W., Molecular cloning of human gastric mucin MUC5AC reveals conserved cysteine-rich D-domains and a putative leucine zipper motif.Biochem. Biophys. Res. Commun., 245, 853–859 (1998).

    Article  PubMed  Google Scholar 

  • van de Graaf, E. A., Out, T. A., Kobesen, A., Jansen, H. M., Lactoferrin and secretory IgA in the bronchoalveolar lavage fluid from patients with a stable asthma.Lung, 169, 275–283 (1991).

    Article  PubMed  Google Scholar 

  • Vogelmeier, C., Hubbard, R. C., Fells, G. A., Schnebli, H. P., Thompson, R. C., Fritz, H., Crystal, R. G., Anti-neutrophil elastase defense of the normal human respiratory epithelial surface provided by the secretory leukoprotease inhibitor.J. Clin. Invest., 87, 482–488 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Voynow, J. A., Selby, D. M., Rose, M. C., Mucin gene expression (MUC1, MUC2, and MUC5/5AC) in nasal epithelial cells of cystic fibrosis, allergic rhinitis, and normal individuals.Lung, 176, 345–354 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Wang, B., Lim, D. J., Han, J., Kim, Y. S., Basbaum, C. B., Li, J. D., Novel cytoplasmic proteins of nontypeable Haemophilus influenzae up-regulate human MUC5AC mucin transcription via a positive p38 mitogen-activated protein kinase pathway and a negative phosphoinositide 3-kinase-Akt pathway.J. Biol. Chem., 277, 949–957 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Wickstrom, C., Davies, J. R., Eriksen, G. V., Veerman, E. C., Carlstedt, I., MUC5B is a major gel-forming, oligomeric mucin from human salivary gland, respiratory tract and endocervix: identification of glycoforms and C-terminal cleavage.Biochem. J., 334, 685–693 (1998).

    PubMed  CAS  Google Scholar 

  • Widdicombe, J. G., Role of lipids in airway function.Eur. J. Respir. Dis., 153, 197–204 (1987).

    CAS  Google Scholar 

  • Williams, S. J., Wreschner, D. H., Tran, M., Eyre, H. J., Sutherland, G. R., McGuckin, M. A., MUC13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells.J. Biol. Chem., 276, 18327–18336 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Wu, R., Yankaskas, J., Cheng, E., Knowles, M. R., Boucher, R., Growth and differentiation of human nasal epithelial cells in culture. Serum-free, hormone-supplemented medium and proteoglycan synthesis.Am. Rev. Respir. Dis., 132, 311–320 (1985).

    PubMed  CAS  Google Scholar 

  • Yoon, J. H., Kim, K. S., Kim, H. U., Linton, J. A., Lee, J. G., Effects of TNF-alpha and IL-1 beta on mucin, lysozyme, IL-6 and IL-8 in passage-2 normal human nasal epithelial cells.Acta Otolaryngol., 119, 905–910 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Yoon, J. H., Kim, K. S., Kim, S. S., Lee, J. G., Park, I. Y., Secretory differentiation of serially passaged normal human nasal epithelial cells by retinoic acid: expression of mucin and lysozyme.Ann. Otol. Rhinol. Laryngoi., 109, 594–601 (2000).

    CAS  Google Scholar 

  • Zhao, J., Sime, P. J., Bringas, P. Jr, Gauldie, J., Warburton, D., Adenovirus-mediated decorin gene transfer prevents TGF-beta-induced inhibition of lung morphogenesis.Am. J. Physiol., 277, L412-L422 (1999).

    PubMed  CAS  Google Scholar 

  • Zrihan-Licht, S., Baruch, A., Elroy-Stein, O., Keydar, I., Wreschner, D. H., Tyrosine phosphorylation of the MUC1 breast cancer membrane proteins. Cytokine receptor-like molecules.FEBS Lettr., 356, 130–136 (1994).

    Article  CAS  Google Scholar 

  • Zuhdi Alimam, M., Piazza, F. M., Selby, D. M., Letwin, N., Huang, L., Rose, M. C., 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).

    PubMed  CAS  Google Scholar 

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Lillehoj, E.P., Kim, K.C. Airway mucus: its components and function. Arch Pharm Res 25, 770–780 (2002). https://doi.org/10.1007/BF02976990

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