• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Mar 1, 1998; 330(Pt 2): 737–744.
PMCID: PMC1219199

Sialomucin complex in the rat respiratory tract: a model for its role in epithelial protection.

Abstract

The pulmonary epithelium has a multitude of specialized functions, which depend on regulated growth and differentiation of several cell types. One such function is the synthesis and secretion of mucins, which offer the epithelium protection from and a means for removal of noxious environmental factors. Sialomucin complex (SMC) is a heterodimeric glycoprotein consisting of a mucin subunit (ASGP-1, ascites sialoglycoprotein-1) and a transmembrane protein (ASGP-2) with two epidermal-growth-factor-like domains. SMC was originally discovered in a highly metastatic rat mammary adenocarcinoma and has been implicated in metastasis and in the protection of the tumour cells from natural killer cells. It can also act as a ligand for the receptor tyrosine kinase 185(neu), suggesting that it is bifunctional as well as heterodimeric. SMC is expressed on the epithelium of rat conducting airways, with the highest levels occurring in the proximal trachea and progressively decreasing into the bronchioles. Airway SMC consists of two forms: a soluble form that lacks the C-terminal cytoplasmic and transmembrane domains and accounts for about 70% of the total, and a membrane-associated form that has the C-terminal domains. Immunocytochemical analyses show that SMC is predominantly present on the apical surfaces of the airway epithelium, but not in goblet cells. Soluble form can be removed from the trachea by rinsing, suggesting that a fraction of the protein is adsorbed to the apical surface. Based on these results, we propose a protective mechanism in which membrane and soluble forms of SMC are produced by airway luminal epithelial cells to provide a cell-associated epithelial glycoprotein barrier that also serves as an interface with flowing mucus. In support of this mechanism, we demonstrated secretion of soluble SMC by primary cultures of tracheal epithelial cells. This model suggests that SMC is a critical element in the protective barrier of the airway epithelium.

Full Text

The Full Text of this article is available as a PDF (418K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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(3-4):289–308. [PubMed]
  • Lamblin G, Aubert JP, Perini JM, Klein A, Porchet N, Degand P, Roussel P. Human respiratory mucins. Eur Respir J. 1992 Feb;5(2):247–256. [PubMed]
  • Sheehan JK, Thornton DJ, Somerville M, Carlstedt I. Mucin structure. The structure and heterogeneity of respiratory mucus glycoproteins. Am Rev Respir Dis. 1991 Sep;144(3 Pt 2):S4–S9. [PubMed]
  • Thornton DJ, Devine PL, Hanski C, Howard M, Sheehan JK. Identification of two major populations of mucins in respiratory secretions. Am J Respir Crit Care Med. 1994 Sep;150(3):823–832. [PubMed]
  • Collins FS. Cystic fibrosis: molecular biology and therapeutic implications. Science. 1992 May 8;256(5058):774–779. [PubMed]
  • Jany B, Basbaum CB. Mucin in disease. Modification of mucin gene expression in airway disease. Am Rev Respir Dis. 1991 Sep;144(3 Pt 2):S38–S41. [PubMed]
  • Jentoft N. Why are proteins O-glycosylated? Trends Biochem Sci. 1990 Aug;15(8):291–294. [PubMed]
  • Carraway KL, Hull SR. Cell surface mucin-type glycoproteins and mucin-like domains. Glycobiology. 1991 Mar;1(2):131–138. [PubMed]
  • Carraway KL, Fregien N, Carraway KL, 3rd, Carraway CA. Tumor sialomucin complexes as tumor antigens and modulators of cellular interactions and proliferation. J Cell Sci. 1992 Oct;103(Pt 2):299–307. [PubMed]
  • Gendler SJ, Spicer AP. Epithelial mucin genes. Annu Rev Physiol. 1995;57:607–634. [PubMed]
  • Codington JF, Frim DM. Cell-surface macromolecular and morphological changes related to allotransplantability in the TA3 tumor. Biomembranes. 1983;11:207–258. [PubMed]
  • Snow LD, Colton DG, Carraway KL. Purification and properties of the major sialoglycoprotein of the milk fat globule membrane. Arch Biochem Biophys. 1977 Mar;179(2):690–696. [PubMed]
  • Ceriani RL, Peterson JA, Lee JY, Moncada R, Blank EW. Characterization of cell surface antigens of human mammary epithelial cells with monoclonal antibodies prepared against human milk fat globule. Somatic Cell Genet. 1983 Jul;9(4):415–427. [PubMed]
  • Patton S, Gendler SJ, Spicer AP. The epithelial mucin, MUC1, of milk, mammary gland and other tissues. Biochim Biophys Acta. 1995 Dec 20;1241(3):407–423. [PubMed]
  • Gendler SJ, Burchell JM, Duhig T, Lamport D, White R, Parker M, Taylor-Papadimitriou J. Cloning of partial cDNA encoding differentiation and tumor-associated mucin glycoproteins expressed by human mammary epithelium. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6060–6064. [PMC free article] [PubMed]
  • Siddiqui J, Abe M, Hayes D, Shani E, Yunis E, Kufe D. Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2320–2323. [PMC free article] [PubMed]
  • Rose MC. Mucins: structure, function, and role in pulmonary diseases. Am J Physiol. 1992 Oct;263(4 Pt 1):L413–L429. [PubMed]
  • Pemberton L, Taylor-Papadimitriou J, Gendler SJ. Antibodies to the cytoplasmic domain of the MUC1 mucin show conservation throughout mammals. Biochem Biophys Res Commun. 1992 May 29;185(1):167–175. [PubMed]
  • Sherblom AP, Carraway KL. A complex of two cell surface glycoproteins from ascites mammary adenocarcinoma cells. J Biol Chem. 1980 Dec 25;255(24):12051–12059. [PubMed]
  • Sherblom AP, Buck RL, Carraway KL. Purification of the major sialoglycoproteins of 13762 MAT-B1 and MAT-C1 rat ascites mammary adenocarcinoma cells by density gradient centrifugation in cesium chloride and guanidine hydrochloride. J Biol Chem. 1980 Jan 25;255(2):783–790. [PubMed]
  • Hull SR, Laine RA, Kaizu T, Rodriguez I, Carraway KL. Structures of the O-linked oligosaccharides of the major cell surface sialoglycoprotein of MAT-B1 and MAT-C1 ascites sublines of the 13762 rat mammary adenocarcinoma. J Biol Chem. 1984 Apr 25;259(8):4866–4877. [PubMed]
  • Wu K, Fregien N, Carraway KL. Molecular cloning and sequencing of the mucin subunit of a heterodimeric, bifunctional cell surface glycoprotein complex of ascites rat mammary adenocarcinoma cells. J Biol Chem. 1994 Apr 22;269(16):11950–11955. [PubMed]
  • Ligtenberg MJ, Kruijshaar L, Buijs F, van Meijer M, Litvinov SV, Hilkens J. Cell-associated episialin is a complex containing two proteins derived from a common precursor. J Biol Chem. 1992 Mar 25;267(9):6171–6177. [PubMed]
  • Ligtenberg MJ, Buijs F, Vos HL, Hilkens J. Suppression of cellular aggregation by high levels of episialin. Cancer Res. 1992 Apr 15;52(8):2318–2324. [PubMed]
  • Sheng Z, Wu K, Carraway KL, Fregien N. Molecular cloning of the transmembrane component of the 13762 mammary adenocarcinoma sialomucin complex. A new member of the epidermal growth factor superfamily. J Biol Chem. 1992 Aug 15;267(23):16341–16346. [PubMed]
  • Carraway KL, Carraway CA, Carraway KL., 3rd Roles of ErbB-3 and ErbB-4 in the physiology and pathology of the mammary gland. J Mammary Gland Biol Neoplasia. 1997 Apr;2(2):187–198. [PubMed]
  • Rossi EA, McNeer RR, Price-Schiavi SA, Van den Brande JM, Komatsu M, Thompson JF, Carraway CA, Fregien NL, Carraway KL. Sialomucin complex, a heterodimeric glycoprotein complex. Expression as a soluble, secretable form in lactating mammary gland and colon. J Biol Chem. 1996 Dec 27;271(52):33476–33485. [PubMed]
  • Wu K, Salas PJ, Yee L, Fregien N, Carraway KL. Tissue and tumor expression of a cell surface glycoprotein complex containing an integral membrane glycoprotein activator of p185neu. Oncogene. 1994 Nov;9(11):3139–3147. [PubMed]
  • Sheng ZQ, Hull SR, Carraway KL. Biosynthesis of the cell surface sialomucin complex of ascites 13762 rat mammary adenocarcinoma cells from a high molecular weight precursor. J Biol Chem. 1990 May 25;265(15):8505–8510. [PubMed]
  • Hull SR, Sheng Z, Vanderpuye O, David C, Carraway KL. Isolation and partial characterization of ascites sialoglycoprotein-2 of the cell surface sialomucin complex of 13762 rat mammary adenocarcinoma cells. Biochem J. 1990 Jan 1;265(1):121–129. [PMC free article] [PubMed]
  • Audie JP, Janin A, Porchet N, Copin MC, Gosselin B, Aubert JP. 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. [PubMed]
  • Thornton DJ, Carlstedt I, Howard M, Devine PL, Price MR, Sheehan JK. Respiratory mucins: identification of core proteins and glycoforms. Biochem J. 1996 Jun 15;316(Pt 3):967–975. [PMC free article] [PubMed]
  • Thornton DJ, Howard M, Khan N, Sheehan JK. 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. [PubMed]
  • Gendler SJ, Lancaster CA, Taylor-Papadimitriou J, Duhig T, Peat N, Burchell J, Pemberton L, Lalani EN, Wilson D. Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. J Biol Chem. 1990 Sep 5;265(25):15286–15293. [PubMed]
  • Wesseling J, van der Valk SW, Vos HL, Sonnenberg A, Hilkens J. Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J Cell Biol. 1995 Apr;129(1):255–265. [PMC free article] [PubMed]
  • Wesseling J, van der Valk SW, Hilkens J. A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1. Mol Biol Cell. 1996 Apr;7(4):565–577. [PMC free article] [PubMed]
  • Goldman MJ, Wilson JM. Expression of alpha v beta 5 integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway. J Virol. 1995 Oct;69(10):5951–5958. [PMC free article] [PubMed]
  • Pickles RJ, Barker PM, Ye H, Boucher RC. Efficient adenovirus-mediated gene transfer to basal but not columnar cells of cartilaginous airway epithelia. Hum Gene Ther. 1996 May 20;7(8):921–931. [PubMed]
  • Hilkens J, Ligtenberg MJ, Vos HL, Litvinov SV. Cell membrane-associated mucins and their adhesion-modulating property. Trends Biochem Sci. 1992 Sep;17(9):359–363. [PubMed]
  • Litt M. Comparative studies of mucus and mucin physicochemistry. Ciba Found Symp. 1984;109:196–211. [PubMed]
  • Wanner A, Salathé M, O'Riordan TG. Mucociliary clearance in the airways. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1868–1902. [PubMed]
  • Kim KC, Nassiri J, Brody JS. 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. [PubMed]
  • Kim KC, Wasano K, Niles RM, Schuster JE, Stone PJ, Brody JS. 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. [PMC free article] [PubMed]
  • Carraway CA, Carvajal ME, Li Y, Carraway KL. Association of p185neu with microfilaments via a large glycoprotein complex in mammary carcinoma microvilli. Evidence for a microfilament-associated signal transduction particle. J Biol Chem. 1993 Mar 15;268(8):5582–5587. [PubMed]
  • Kokai Y, Cohen JA, Drebin JA, Greene MI. Stage- and tissue-specific expression of the neu oncogene in rat development. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8498–8501. [PMC free article] [PubMed]
  • Press MF, Cordon-Cardo C, Slamon DJ. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene. 1990 Jul;5(7):953–962. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...