Ciba Foundation Symposium 109 - Mucus and Mucosa

255 Pages·1984·13.228 MB·English

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