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. 2000;9(6):277–284. doi: 10.1080/09629350020027582

ATP induced MUC5AC release from human airways in vitro.

P Roger 1, J P Gascard 1, J Bara 1, V T de Montpreville 1, M Yeadon 1, C Brink 1
PMCID: PMC1781772  PMID: 11213911

Abstract

BACKGROUND: Chronic airway diseases are often associated with marked mucus production, however, little is known about the regulation of secretory activity by locally released endogenous mediators. AIM: This investigation was performed to determine the release of MUC5AC mucin from human bronchial preparations using the purinergic agonists adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP). METHODS: Immunohistochemical and immunoradiometric assays (IRMA) were used to detect the MUC5AC mucin. Immunohistochemical analysis were performed using individual 1-13 M1 and 21 M1 MAbs recognizing a recombinant M1 mucin partially encoded by the MUC5AC gene. IRMA measurments were performed using a mixture of eight anti-M1 mucin MAbs (PM8), which included both 1-13 M1 and 21 M1 MAbs. Lysozyme and protein were also measured in the biological fluids derived from human bronchial preparations obtained from patients who had undergone surgery for lung carcinoma. RESULTS: The anti-M1 monoclonal antibodies labelled epithelial goblet cells. After challenge of human bronchial preparations with ATP, the goblet cells exhibited less staining. In contrast, UTP did not alter the immunolabelling of goblet cells. MUC5AC mucin in the bronchial fluids derived from ATP-challenged preparations was increased while UTP had no effect on release. ATP did not alter either the quantities of lysozyme or protein detected in the biological fluids. CONCLUSION: These results suggest that ATP may regulate epithelial goblet cell secretion of MUC5AC mucin from human airways in vitro.

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Selected References

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  1. Adler K. B., Akley N. J., Glasgow W. C. Platelet-activating factor provokes release of mucin-like glycoproteins from guinea pig respiratory epithelial cells via a lipoxygenase-dependent mechanism. Am J Respir Cell Mol Biol. 1992 May;6(5):550–556. doi: 10.1165/ajrcmb/6.5.550. [DOI] [PubMed] [Google Scholar]
  2. Adler K. B., Fischer B. M., Li H., Choe N. H., Wright D. T. Hypersecretion of mucin in response to inflammatory mediators by guinea pig tracheal epithelial cells in vitro is blocked by inhibition of nitric oxide synthase. Am J Respir Cell Mol Biol. 1995 Nov;13(5):526–530. doi: 10.1165/ajrcmb.13.5.7576687. [DOI] [PubMed] [Google Scholar]
  3. Audie J. P., Janin A., Porchet N., Copin M. C., Gosselin B., Aubert J. P. Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization. J Histochem Cytochem. 1993 Oct;41(10):1479–1485. doi: 10.1177/41.10.8245407. [DOI] [PubMed] [Google Scholar]
  4. Bara J., Chastre E., Mahiou J., Singh R. L., Forgue-Lafitte M. E., Hollande E., Godeau F. Gastric M1 mucin, an early oncofetal marker of colon carcinogenesis, is encoded by the MUC5AC gene. Int J Cancer. 1998 Mar 2;75(5):767–773. doi: 10.1002/(sici)1097-0215(19980302)75:5<767::aid-ijc17>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  5. Bara J., Gautier R., Daher N., Zaghouani H., Decaens C. Monoclonal antibodies against oncofetal mucin M1 antigens associated with precancerous colonic mucosae. Cancer Res. 1986 Aug;46(8):3983–3989. [PubMed] [Google Scholar]
  6. Bara J., Gautier R., Le Pendu J., Oriol R. Immunochemical characterization of mucins. Polypeptide (M1) and polysaccharide (A and Leb) antigens. Biochem J. 1988 Aug 15;254(1):185–193. doi: 10.1042/bj2540185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chan H. C., Zhou W. L., Fu W. O., Ko W. H., Wong P. Y. Different regulatory pathways involved in ATP-stimulated chloride secretion in rat epididymal epithelium. J Cell Physiol. 1995 Aug;164(2):271–276. doi: 10.1002/jcp.1041640207. [DOI] [PubMed] [Google Scholar]
  8. Davis C. W., Dowell M. L., Lethem M., Van Scott M. Goblet cell degranulation in isolated canine tracheal epithelium: response to exogenous ATP, ADP, and adenosine. Am J Physiol. 1992 May;262(5 Pt 1):C1313–C1323. doi: 10.1152/ajpcell.1992.262.5.C1313. [DOI] [PubMed] [Google Scholar]
  9. 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. 1994 Jul-Aug;20(4):367–380. doi: 10.3109/01902149409064393. [DOI] [PubMed] [Google Scholar]
  10. Hovenberg H. W., Davies J. R., Herrmann A., Lindén C. J., Carlstedt I. MUC5AC, but not MUC2, is a prominent mucin in respiratory secretions. Glycoconj J. 1996 Oct;13(5):839–847. doi: 10.1007/BF00702348. [DOI] [PubMed] [Google Scholar]
  11. Kim K. C., Nassiri J., Brody J. S. Mechanisms of airway goblet cell mucin release: studies with cultured tracheal surface epithelial cells. Am J Respir Cell Mol Biol. 1989 Aug;1(2):137–143. doi: 10.1165/ajrcmb/1.2.137. [DOI] [PubMed] [Google Scholar]
  12. 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 U S A. 1987 Dec;84(24):9304–9308. doi: 10.1073/pnas.84.24.9304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kim K. C., Zheng Q. X., Van-Seuningen I. Involvement of a signal transduction mechanism in ATP-induced mucin release from cultured airway goblet cells. Am J Respir Cell Mol Biol. 1993 Feb;8(2):121–125. doi: 10.1165/ajrcmb/8.2.121. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Labat C., Bara J., Gascard J. P., Sossé-Alaoui H., Thomas de Montpreville V., Yeadon M., Brink C. M1/MUC5AC mucin released by human airways in vitro. Eur Respir J. 1999 Aug;14(2):390–395. doi: 10.1034/j.1399-3003.1999.14b25.x. [DOI] [PubMed] [Google Scholar]
  16. Lethem M. I., Dowell M. L., Van Scott M., Yankaskas J. R., Egan T., Boucher R. C., Davis C. W. Nucleotide regulation of goblet cells in human airway epithelial explants: normal exocytosis in cystic fibrosis. Am J Respir Cell Mol Biol. 1993 Sep;9(3):315–322. doi: 10.1165/ajrcmb/9.3.315. [DOI] [PubMed] [Google Scholar]
  17. Logun C., Mullol J., Rieves D., Hoffman A., Johnson C., Miller R., Goff J., Kaliner M., Shelhamer J. Use of a monoclonal antibody enzyme-linked immunosorbent assay to measure human respiratory glycoprotein production in vitro. Am J Respir Cell Mol Biol. 1991 Jul;5(1):71–79. doi: 10.1165/ajrcmb/5.1.71. [DOI] [PubMed] [Google Scholar]
  18. Montserrat C., Merten M., Figarella C. Defective ATP-dependent mucin secretion by cystic fibrosis pancreatic epithelial cells. FEBS Lett. 1996 Sep 16;393(2-3):264–268. doi: 10.1016/0014-5793(96)00900-3. [DOI] [PubMed] [Google Scholar]
  19. Niles R. M., Christensen T. G., Breuer R., Stone P. J., Snider G. L. Serine proteases stimulate mucous glycoprotein release from hamster tracheal ring organ culture. J Lab Clin Med. 1986 Nov;108(5):489–497. [PubMed] [Google Scholar]
  20. PETIT J. F., JOLLES P. PURIFICATION AND ANALYSIS OF HUMAN SALIVA LYSOZYME. Nature. 1963 Oct 12;200:168–169. doi: 10.1038/200168a0. [DOI] [PubMed] [Google Scholar]
  21. Reid C. J., Gould S., Harris A. Developmental expression of mucin genes in the human respiratory tract. Am J Respir Cell Mol Biol. 1997 Nov;17(5):592–598. doi: 10.1165/ajrcmb.17.5.2798. [DOI] [PubMed] [Google Scholar]
  22. Roger P., Gascard J. P., de Montpreville V. T., Brink C. Basal secretion of lysozyme from human airways in vitro. Mediators Inflamm. 1999;8(6):319–323. doi: 10.1080/09629359990333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schulman E. S., Glaum M. C., Post T., Wang Y., Raible D. G., Mohanty J., Butterfield J. H., Pelleg A. ATP modulates anti-IgE-induced release of histamine from human lung mast cells. Am J Respir Cell Mol Biol. 1999 Mar;20(3):530–537. doi: 10.1165/ajrcmb.20.3.3387. [DOI] [PubMed] [Google Scholar]
  24. Shankar V., Pichan P., Eddy R. L., Jr, Tonk V., Nowak N., Sait S. N., Shows T. B., Schultz R. E., Gotway G., Elkins R. C. Chromosomal localization of a human mucin gene (MUC8) and cloning of the cDNA corresponding to the carboxy terminus. Am J Respir Cell Mol Biol. 1997 Mar;16(3):232–241. doi: 10.1165/ajrcmb.16.3.9070607. [DOI] [PubMed] [Google Scholar]
  25. Shimura S., Sasaki T., Nagaki M., Takishima T., Shirato K. Extracellular ATP regulation of feline tracheal submucosal gland secretion. Am J Physiol. 1994 Aug;267(2 Pt 1):L159–L164. doi: 10.1152/ajplung.1994.267.2.L159. [DOI] [PubMed] [Google Scholar]
  26. Shin C. Y., Kim K. C., Lee W. J., Jo M. J., Park K. H., Dalby R., Ko K. H. Inhaled ATP causes mucin release from goblet cells of intact rats. Exp Lung Res. 2000 Jan-Feb;26(1):1–11. doi: 10.1080/019021400269925. [DOI] [PubMed] [Google Scholar]
  27. Sossé-Alaoui H., Labat C., Gorenne I., Thomas de Montpreville V., Bara J., Brink C. Glycoconjugate secretion in human airways in vitro: effects of epithelium removal. Mediators Inflamm. 1998;7(1):25–30. doi: 10.1080/09629359891342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Thornton D. J., Howard M., Khan N., Sheehan J. K. Identification of two glycoforms of the MUC5B mucin in human respiratory mucus. Evidence for a cysteine-rich sequence repeated within the molecule. J Biol Chem. 1997 Apr 4;272(14):9561–9566. doi: 10.1074/jbc.272.14.9561. [DOI] [PubMed] [Google Scholar]
  29. Webber S. E. The effects of peptide histidine isoleucine and neuropeptide Y on mucus volume output from the ferret trachea. Br J Pharmacol. 1988 Sep;95(1):49–54. doi: 10.1111/j.1476-5381.1988.tb16547.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. van den Ingh H. F., Bara J., Cornelisse C. J., Nap M. Aneuploidy and expression of gastric-associated mucus antigens M1 and CEA in colorectal adenomas. Am J Clin Pathol. 1987 Feb;87(2):174–179. doi: 10.1093/ajcp/87.2.174. [DOI] [PubMed] [Google Scholar]

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