Abstract
Airway mucus hypersecretion occurs in response to infection and irritation and poses an important and poorly understood clinical problem. In order to gain insight into its pathogenesis, we have focused on an mRNA encoding the major mucus glycoprotein, mucin. Northern blots showed that mucin mRNA was abundant in the intestine of specific pathogen free rats whereas it was undetectable in the airways of these rats until pathogen-free conditions were suspended and rats acquired Sendai (Parainfluenza I) virus infections. Airway mucin hybridization signals in rats that were both infected with Sendai virus and exposed to SO2were more intense than those in rats with infection alone. These results suggest that pathogen-and irritant-induced hypersecretion may be partly controlled at the level of mucin mRNA.
References
- 1.A.T.S. Chronic bronchitis, asthma, and pulmonary emphysema. Am. Rev. Respir. Dis. 1962;85:762–768. [Google Scholar]
- 2.Reid LM. Pathology of chronic bronchitis. Lancet. 1954;1:275–278. [PubMed] [Google Scholar]
- 3.Aikawa T, Shimura S, Sasaki H, Takishima T, Yaegashi H, Takahashi T. Morphometric analysis of intraluminal mucus in airways in chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 1989;140:477–482. doi: 10.1164/ajrccm/140.2.477. [DOI] [PubMed] [Google Scholar]
- 4.Hogg JC, Macklem PT, Thurlbeck WM. Site and nature of airway obstruction in chronic obstructive lung disease. New England Journal of Medicine. 1968;278:1355–1360. doi: 10.1056/NEJM196806202782501. [DOI] [PubMed] [Google Scholar]
- 5.Darnell JE. Variety in the level of gene control in eukaryotic cells. Nature. 1982;297:365–371. doi: 10.1038/297365a0. [DOI] [PubMed] [Google Scholar]
- 6.Jany B, Gallup M, Basbaum C. Parainfluenza I virus: a possible trigger for mucin gene expression in rat airways. Am. Rev. Respir. Dis. 1991;143:A135. [Google Scholar]
- 7.Lamb D, Reid L. Mitotic rates, goblet cell increase and histochemical changes in mucus in rat bronchial epithelium during exposure to sulphur dioxide. Journal of Pathology & Bacteria. 1968;96:97–111. doi: 10.1002/path.1700960111. [DOI] [PubMed] [Google Scholar]
- 8.U.S. Department of Health, Education and Welfare, Publication # (NIOSH); 1974. Occupational exposure to sulfuric acid; pp. 74–128. [Google Scholar]
- 9.Chomczynski P, Sachi N. Single step methods of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 1987;162:156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- 10.Gum JR, Byrd JC, Hicks JW, Toribara NW, Lamport DTA, Kim YS. Molecular cloning of human intestinal mucin cDNAs. J. Biol. Chem. 1989;264:6480–6487. [PubMed] [Google Scholar]
- 11.Timpte CS, Eckhardt AE, Abernethy JL, Hill RL1. Porcine submaxillary gland apomucin contains tandemly repeated identical sequences of 81 residues. J. Biol. Chem. 1988;263:1081–1088. [PubMed] [Google Scholar]
- 12.Gendler SJ, Burchell JM, Duhig T, White R, Parker M. Vol. 84. 1987. Cloning of partial cDNA encoding differentiation and tumour-associated mucin glycoproteins expressed by human epithelium; pp. 6060–6064. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Siddiqui J, Abe M, Hayes D, Shani E, Yunis E, Kufe D. Vol. 85. 1988. Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen; pp. 2320–2323. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Gendler S, Taylor-Papadimitriou J, Duhig T, Rothbard J, Burchell J. A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats. J. Biol. Chem. 1988;263:12820–12823. [PubMed] [Google Scholar]
- 15.Neutra MR, Forster JF. Editor, Raven Press; 1987. Gastrointestinal mucus: Synthesis, secretion, and function. [Google Scholar]
- 16.Woodward H, Horsey B, Bhavanandan P, Davidson EA. Isolation, purification, and properties of respiratory mucus glycoproteins. Biochem. 1982;21:694–701. doi: 10.1021/bi00533a017. [DOI] [PubMed] [Google Scholar]
- 17.Chace KV, Flux M, Sachdev GP. Comparison of physicochemical properties of purified mucus glycoproteins isolated from respiratory secretions of cystic fibrosis and asthmatic patients. Biochem. 1985;24:7334–7341. doi: 10.1021/bi00346a047. [DOI] [PubMed] [Google Scholar]
- 18.Perini JM, Marianne T, Lafitte JJ, Lamblin G, Roussel P, Mazzuca M. Use of an antiserum against deglycosylated human mucins for cellular localization of their peptide precursors: Antigenic similarities between bronchial and intestinal mucins. J. Histochem. Cytochem. 1989;37:869–875. doi: 10.1177/37.6.2470810. [DOI] [PubMed] [Google Scholar]
- 19.Jany B, Gallup M, Yan PS, Gum J, Kim Y, Basbaum C. Human intestine and airways express the same mucin gene. J. Clin. Invest. 1991;87:77–82. doi: 10.1172/JCI115004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Gum JR, Hicks JW, Swallow DM, Lagace RL, Byrd JC, Lamport DTA, Siddiki B, Kim YS. Molecular cloning of cDNAs derived from a novel human intestinal mucin gene. Biochem. & Biophy. Res. Comm. 1990;171:407–415. doi: 10.1016/0006-291x(90)91408-k. [DOI] [PubMed] [Google Scholar]
- 21.Marianne T, Perini J-M, Lafitte J-J, Houdret N, Pruvot F-R, Lamblin G, Slayter HS, Roussel P. Peptides of human bronchial mucus glycoproteins. Biochem. J. 1987;248:189–195. doi: 10.1042/bj2480189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Huang HT, Haskell A, McDonald DM. Changes in epithelial secretory cells and potentiation of neurogenic inflammation in the trachea of rats with respiratory tract infections. Anat. Embryol. 1989;180:325–341. doi: 10.1007/BF00311165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Plopper CG, Mariassy AT, Wilson DW, Alley JL, Nishio SJ, Nettesheim P. Comparison of nonciliated tracheal epithelial cells in six mammalian species: Ultrastructure and population densities. Exp. Lung Res. 1983;5 doi: 10.3109/01902148309061521. [DOI] [PubMed] [Google Scholar]
- 24.Koshino T, Bhaskar R, Reid LM, Gerard C, Warner A, Shore SA, Anderson K, Butler G, Iijima H, Drazen MM. Recovery of an epitope recognized by a monoclonal antibody from airway lavage during experimental induction of chronic bronchitis. American Journal of Respiratory Cell & Molecular Biology. 1990;2:453–462. doi: 10.1165/ajrcmb/2.5.453. [DOI] [PubMed] [Google Scholar]
- 25.Bhaskar KR, Drazen JM, O'Sullivan DD, Scanlon PM, Reid LM. Transition from normal to hypersecretory bronchial mucus in a canine model of bronchitis: Chances in yield and composition. Exp. Lung Res. 1988;14:101–120. doi: 10.3109/01902148809062853. [DOI] [PubMed] [Google Scholar]
- 26.Bhaskar KR, O'Sullivan DD, Seltzer J, Rossing TH, Drazen JM, Reid LM. Density gradient study of bronchial mucus aspirates from healthy volunteers (smokers and nonsmokers) and from patients with tracheostomy. Exp. Lung Res. 1985;9:289–308. doi: 10.3109/01902148509057529. [DOI] [PubMed] [Google Scholar]
- 27.Castleman WL. Respiratory tract lesions in weanling outbred rats infected with sendai virus. Am. J. Vet. Res. 1983;44:1024–1031. [PubMed] [Google Scholar]
- 28.Castleman WL. Alterations in pulmonary ultrastructure and morphometric parameters induced by parainfluenza (sendai) virus in rats during postnatal growth. Am. J. Pathol. 1984;114:322–335. [PMC free article] [PubMed] [Google Scholar]
- 29.Giddens WE, Hoosier GL, Garlinghouse LE. Experimental sendai virus infections in laboratory rats II. Pathology and immunohistochemistry. Lab. Animal Sci. 1987;37:442–448. [PubMed] [Google Scholar]
- 30.Smith CWJ, Patton JG, Nadal-Ginard B. Alternative splicing in the control of gene expression. Annu. Rev. Genet. 1989;23:527–577. doi: 10.1146/annurev.ge.23.120189.002523. [DOI] [PubMed] [Google Scholar]
- 31.Ross J. Messenger RNA turnover in eukaryotic cells. Mol. Biol. Med. 1988;5:1–14. [PubMed] [Google Scholar]
- 32.Lamb D, Reid L. Goblet cells increase in rat bronchial epithelium after exposure to cigarette and cigar smoke. Brit. Med. J. 1969;1:33–35. doi: 10.1136/bmj.1.5635.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Royce FA, Basbaum CB. Analysis of thymidine incorporation by airway epithelial cells in a rat model of chronic bronchitis. Am. Rev. Respir. Dis. 1990;141:A107. [Google Scholar]
- 34.Ayers MM, Jeffery PK. Cellular Biology of the Lung. G. Bonsignore and G. Cummings, Plenum Press; New York: 1982. Cell division and differentiation in bronchial epithelium. [Google Scholar]
- 35.Shan B, Lewis JA. Interferon-induced expression of different genes is mediated by distinct regulatory pathways. 1989;170:277–281. doi: 10.1016/0042-6822(89)90378-4. [DOI] [PubMed] [Google Scholar]
- 36.Harkema JR, Hotchkiss JA, Harmsen AG, Henderson RF. Am. J. Pathol. 1988;130:605. [PMC free article] [PubMed] [Google Scholar]
- 37.Christensen TG, Korthy AL, Snider GL, Hayes JA. Irreversible bronchial goblet cell metaplasia in hamsters with elastase-induced panacinar emphysema. J. Clin. Invest. 1977;59:397–404. doi: 10.1172/JCI108652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Basbaum C, Jany B. Plasticity in the airway epithelium. Am. J. Physiol. 1990;259:L38–L46. doi: 10.1152/ajplung.1990.259.2.L38. [DOI] [PubMed] [Google Scholar]