Mucus and mucosa The Ciba Foundation is ;in international scientific and educational charity. It wits established in 1947 by the Swiss chemical and pharmaccutical company of CIBA Limited. -now CIBA-GEIGY Limited. The Foundation operates independcntly in London under English trust law. The Ciba Foundation cxists to promote international cooperation in hiological. medical and chemical research. It organizes about eight international multidisciplin topics that wem ready for disc .ion by ;I small group of' research discussions arc published in the ha Foundation bymposium series. Thc t.oundution also holds many shorter meetings (not published). organized by the Foundation itsell or by outside scicntific organizations. The staff always welcome suggestions for future meetings. The Foundation's housc at JI Portland Place. London W1N JRN, provides lacilitics lor a11 the meetings. Its library. open seven days a week to any gr;iduate in sciencc or medicine, also provides information on scicntilic meetings throughout the world and answers general enquiries on biomedical and chemical suhjects. Scientists from any part of the world may stay in the house during working visits to London. Mucus and mucosa Ciba Foundation symposium 109 1984 Pitman London 0C iba Foundation 1984 ISBN 0 212 79783 9 Published in November 1984 by Pitman Publishing Ltd. 128 Long Acre, London WC2E 9AN. UK Distributed in North America by Ciba Pharmaceutical Company (Medical Education Division). P.O. Box 12832, Newark. NJ 07101. USA Suggested series entry for library catalogues: Ciba Foundation symposia Ciba Foundation symposium 109 + ix 246 pages. 40 figures, 23 tables British Library Cataloguing in Publication Data Mucus and mucosa.-(Ciba Foundation symposium; 109) I. Mucuh I. Nugent. Jonathan 11. O‘Connor. Maeve 111. Serieh 61 l’.Ol81 OP215 Printed in Great Britain at The Pitman Press. Bath Con tents Symposium on Mucus arid mucosa, held at the Ciba Foundation, London, 28 February-I March 1984 Editors: Jonathan Nugent (Organizer) arid Maeve O’Connor A. Silberberg Introduction 1 C. B. Basbaum Regulation of secretion from serous and mucous cells in the trachea 4 Discussion 1.5 M. R. Neutra, T. L. Phillips and T. E. Phillips Regulation of intestinal goblet cells in situ, in mucosal explants and in the isolated epithelium 20 Discussion 29 S. J. Coles, K. R. Bhaskar, D. D. O’Sullivan, K. H. Neil1 and L. M. Reid Airway mucus: composition and regulation of its secretion by neuropeptides in vitro 40 Discussion 54 J. Forstner, N. Roomi, R. Fahim, G. Gall, M. Perdue and G. Forstner Acute and chronic models for hypersecretion of intestinal mucin 61 Discussion 68 T. F. Boat, P. W. Cheng, T. D. Klinger, C. M. Liedtke and B. Tandler Proteinases release mucin from airways goblet cells 72 Discussion 84 General Discussion Regulation of mucus secretion 89 G. Flemstrom and A. Garner Some characteristics of duodenal epithelium 94 Discussion 105 J. H. Widdicombe Fluid transport across airway epithelia 109 Discussion 117 V vi CONTENTS J. R. Clamp and J. M. Creeth Some non-mucin components of mucus and their possible biological roles 121 Discussion 131 A. Allen, D. A. Hutton, J. P. Pearson and L. A. Sellers Mucus glycoprotein structure, gel formation and gastrointestinal mucus function 137 Discussion 15 1 I. Carlstedt and J. K. Sheehan Macromolecular properties and polymeric structure of mucus glycoproteins 157 Discussion 166 M. Elstein and G. M. Fawcett Effects of the anti-oestrogens, clomiphene and tamoxifen, on the cervical factor in female infertility 173 E. N. Chantler and P. R. Scudder Terminal glycosylation in human cervical mucin 180 Discussion of the two preceding papers 188 M. Litt Comparative studies of mucus and mucin physicochemistry 196 Discussion 206 P. Verdugo Hydration kinetics of exocytosed mucins in cultured secretory cells of the rabbit trachea: a new model 212 Discussion 222 Final general discussion Mucus swelling, secretion and effects on cilia 226 Epithelial preparations 229 A. Silberberg Closing remarks 235 Index of contributors 237 Subject index 238 Participants A. Allen Department of Physiological Sciences. University of Newcastle upon Tyne, Medical School, Newcastle upon Tyne NE1 7RU, UK C. B. Basbaum Department of Anatomy and Cardiovascular Research Institute, 1315-M, University of California-San Francisco, San Francisco, CA 94143, USA J. Bilski (Ciha Foundafion Bursar) Institute of Physiology, Nicolaus Coper- nicus Academy of Medicine, 31-531 Krakow, Grzegorzecka 16, Poland T. F. Boat Department of Pediatrics, University of North Carolina at Chapel Hill, Medical School, Burnett-Womack Clinical Sciences Bldg 229H, Chapel Hill, North Carolina 27514, USA I. Carlstedt Department of Physiological Chemistry 2, University of Lund, P 0 Box 750, S-220 07 Lund 7, Sweden E. Chantler Department of Obstetrics & Gynaecology, University of Man- Chester, University Hospital of South Manchester, West Didsbury, Manchester M20 8LR, UK J. R. Clamp Department of Medicine, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW, UK S. Coles Department of Pathology, Harvard Medical School, Children’s Hospital Medical Center, 300 Longwood Avenue, Boston, MA 02115, USA (Present address: Medical Department, Abbott Laboratories, Queen- borough, Kent ME11 5EL, UK) J. M. Creeth Department of Medicine, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW, UK M. Elstein Department of Obstetrics & Gynaecology, University of Man- Chester, University Hospital of South Manchester, West Didsbury, Manchester M20 8LR, UK vii ... Vlll PARTICIPANTS G. Flemstrom Department of Physiology 8( Medical Biophysics, University of Uppsala, Biomedical Center, P 0 Box 572. S-751 23 Uppsala. Sweden G. Forstner Department of Paediatrics, Physiology, University of Toronto, Hospital for Sick Children, Research Institute, 555 University Avenue, Toronto, Ontario M5G 1x8, Canada J. Forstner Division of Biochemistry, Hospital for Sick Children, Research Institute, 555 University Avenue, Toronto, Ontario M5G 1x8. Canada A. Garner Bioscience Department, Pharmaceuticals Division, ICI plc, Mereside, Alderley Park, Macclesfield, Cheshire SKlO 4TG, UK P. W. Kent Nuffield Department of Clinical Biochemistry, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK M. Litt Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, 285 Towne/D3, 220 South 33rd Street, Philadelphia, PA 19104, USA C. Marriott Department of Pharmacy, Brighton Polytechnic, Moulse- coomb, Brighton, Sussex BN2 4GJ, UK J. A. Nadel Cardiovascular Research Institute, 1315-M, University of California-San Francisco, San Francisco, CA 94143, USA M. Neutra Department of Anatomy, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA L. M. Reid Department of Pathology, Harvard Medical School, Children's Hospital Medical Center, 300 Longwood Avenue, Boston, MA 021 15, USA P. S. Richardson Department of Physiology, St George's Hospital Medical School, Cranmer Terrace, Tooting, London SW17 ORE, UK P. Roussel Department of Biochemistry, Protein Unit, INSERM, (No. 16), Place de Verdun, 59045 Lille Cedex, France A. Silberberg (Chairman) Department of Polymer Research, The Weiz- mann Institute of Science, IL-76100 Rehovot, Israel PARTICIPANTS ix P. Verdugo Center for Bioengineering, WD-12, University of Washington School of Medicine, Seattle, Washington 98195, USA J. G. Widdicombe Department of Physiology, St George’s Hospital Medical School, Cranmer Terrace, Tooting, London SW17 ORE, UK J. H. Widdicombe Department of Physiology and Cardiovascular Research Institute, 1315-M, University of California-San Francisco, San Francisco, CA 94143, USA Introduction A. SILBERBERG Department of’ Polymer Keseurch. The Weizrriurin Iti.siiiuie of Science, 76/00 Rehovor. 1,srueI It is an honour and pleasure to have been asked to preside at this meeting. Let me emphasize a few points. Firstly, in general terms, what we would like to achieve here is the generation of ideas ideas that will not necessarily be - fully expressed in the printed proceedings, but that each of us can take back and attribute to this symposium. However, if we have a good and fruitful discussion, it may help to inspire those who later read the book. Secondly, during the last few months, I have asked most of the participants for their views on what the main topics of our discussion should be - not so much their own personal interests, but what they felt could be usefully discus- sed by this group. There was a strong consensus that the link between the structure and function of mucus should be discussed. Knowing the one would help us to understand the other, or to generate ideas about the other. So this, I hope, will be one very important focus of our discussions. It is intriguing, in this connection, that most of the papers do not address function directly, but only indirectly. Structure is more kindly dealt with on the whole. Here, of course, there is agreement. There is little doubt today that mucus is a loose gel involving a network composed of a typical, repeating glycoprotein moiety. These units are held together by two kinds of cross-links. One kind of link strings the glycoprotein moieties into a chain, and these may be very long chains - a polymerization type of interaction. The other kind of link ties the polymerized strands together into the network, i.e. establishes the gel-forming cross-links. We know very little about either of these links, howev- er. They may, indeed, be of many kinds. In particular, they may or may not be covalent. They may also involve other macromolecules. But certainly for the gel to possess the functional properties it has, such bonds must have life-times of minutes or seconds at least. These are long times in relation to the life-time of a normal secondary bond, so we must expect that if the cross-links are secon- dary, they must be endowed with very special properties. For example, they 1984 Mucus and mucosu. Pitman, London (Ciha Foundulion symposium 109) p 1-3 1