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About
màj 23/07/98 |
Report
by Claire Abbal on the following session :
Samedi 14 Février 1998
|
Présentateurs
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Modérateurs
|
Experts
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11h00-12h00
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Réparation bronchique
Bronchial
remodelling
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C. Lafuma
(Paris)
G.
Mautino (Montpellier)
Discussion
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15'
15' 30'
|
J.
Bousquet (Montpellier)
D. Olivieri (Parme, I)
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J.
Shute (Southampton, UK)
L. Fabbri (Ferrara, I)
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Discussion
J. Shute : Did you look
at the cell source of MMP-9 in the epithelium,
particularly was there a difference between basal cells
and upper cells ?
C. Lafuma : We have only investigated primary culture of
bronchial epithelial cells from bronchial explants and
there were composed of many types of cells, resident
cells and cells that
have migrated. So it was impossible to distinguish
between them on the basis of their level of MMP-9
production.
J. Shute : high degree of
MMP-9, as well as stromelysin-1, in status asthmatic are
interesting as it is not observed in mild asthma. Can you
comment on the source of the stromelysin ?
C. Lafuma : Stromelysin-1, that could be a strong
activator of gelatinases, possibly comes from epithelial
cells because we detect it in our primary culture of
bronchial respiratory cells.
J. Shute : Your
hypothesis is that MMP-9 degradates desmosomal proteins.
Do you have evidence of that ?
C. Lafuma : We have an animal model of bronchial
hyperresponsiveness which consists in the injection of
gas molecules in rat to investigate wether MMP-9 is
released, and we have found an expression of MMP-9 localised at the basal site of epithelium
and this could mean that there will be a desmosome
destruction.
|
L. Fabbri : Why did you look at alveolar macrophages since
your hypothesis was that
metalloproteinases are involved in the airway wall remodelling ? Could you look, in the future, at
the differential expression of metalloproteinases and inhibitors
in alveolar macrophages and in interstitiel macrophages?
G. Mautino : Thiswork is in
progress since we will investigate these proteins in bronchial
biopsies using in situ
hybridization and immunohistochemistry.
L. Fabbri : You correctly compare
normal patients versus mild asthmatic versus severe asthmatic
versus patients with chronic bronchitis, why did
you expect to have different type and quantity of remodelling in vivo?
G. Mautino : it is a question of TIMP-1/MMP-9 balance in these
different groups but the results we have obtained in
bronchoalveolar lavages are too preliminar to be discussed now.
M. Vignola : we have measured
MMP-9 and TIMP-1 in sputum of untreated asthmatic patients and
COPD patients, we have found that there was an increase in TIMP-1
levels with respect to MMP-9 levels in patients with more severe
asthma than in mild asmatic patients and there was a direct
correlation between this ratio and the degree of airway
obstruction. So, one hypothesis will be that higher is the level
of TIMP-1, higher is the risk to increase airway remodelling in these patients because of the
increased amount of collagen which is accumulated in the airway
wall.
L. Fabbri : There is different
amount of remodelling in the
airways of asthmatics and COPD patients and I think there is also
a different distribution of the remodelling. It looks like in the most severe asthmatics you have a central
airway remodelling in
addition to a peripheral airway remodelling. So this question must be addressed
topically.
J. Bousquet : The greater
TIMP-1/MMP-9 ratio suggests that there is an increased
remodelling of airways in patients with severe asthma. However, C Lafuma showed that in acute asthma there is a higher gelatinolytic activity. So there is
probably a fine regulation between MMPs and TIMPs in the airway
depending on the state of asthma and as well depending on the
exacerbation rate.
M. Vignola : We need some
measurement to quantify the amount of airway remodelling, FEV-1
perhaps does not reflect the airway remodelling. But, to date, we
have no way to clearly understand the clinical impacts of the
airway remodelling. I think that imaging might help us in
detecting the morphology of the airways and measuring the
alteration of the bronchial wall in patients who seem to be
characterized by airway remodelling.
L. Fabbri : About the nice
correlation between MMP-9 and albumin can you reproduce it in an
animal model ?
C. Lafuma : We have a model of acute lung edema induced by
intratracheal injection of LPS in rat, and we observed an
increase of MMP-9 in BAL and
this was correlated with the increase of albumin.
Dr. Rabe : Do you have any information on people
who just have high level of neutrophils once or
repeatively in their history and do
you think that, what you have
measured, and, mechanisms leaded to airway remodelling
is specific of asthma?
C. Lafuma : In cystic fibrosis there is an important increase of
neutrophils and we observed that there is an acute expression of
MMP-9 in the sputum. This excess of gelatinase is higher than its
inhibitor TIMP-1 as we have observed in patients with Status
Asmaticus.
J. Bousquet : I do not think
there is a specificity. Not only epithelial cells, neutrophils,
macrophages but also eosinophils were shown to be involved in the
processing of MMPs and TIMPs generation. So, it is a far more
complex situation than it would be if a simple new protein would
have been discovered in asthma.
. 
Enfumosa Congrès Conçue et réalisée par: Michel Godard (at) Top
Date de création: 12 Février 1998 -Dernière mise à jour: 23/07/98
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