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màj 23/07/98
ENFUMOSA
(courriel: Chanez (at) montp.inserm.fr )
The European Network For Understanding
Mechanisms of Severe Asthma
BIOMED 2 Program - European Commission

4th quaterly meeting, with the support of INSERM and
Merck Sharp & Dohme Laboratory
February 13-14th 1998 in Montpellier- France
(see programm, abstracts and experts comments )

Report by S. Matecki on the following session :

Samedi 14 Février 1998

Présentateurs

Modérateurs

Experts

8h30-9h30

Muscle lisse

Smooth muscle

M. Molimard (Paris)
J.M. Tunon de Lara (Bordeaux)
Discussion

15' 15' 30'

R. Marthan (Bordeaux)
J. Mercier (Montpellier)

F.P. Nijkamp (Utrecht, NL)
K. Rabe (Grossandorf, D)

M. Molimard spoke about the influence of lipopolysaccharide (LPS) and Interleukine 1-ß (IL1-ß) on human isolated bronchi responsiveness to bradykinin, substance-P and neurokinine A.

LPS and IL1-ß involved in the inflammatory response, enhance in vitro the contraction of human isolated bronchus response to bradykinin. This effect is time dependent, and it is abolished by indomethacin. This inhibition exist also with thromboxane A2 antagonist and bradykinin B2 receptor antagonist. It seemed that responsiveness to bradykinin was mediated by thromboxane receptor stimulation. But the cyclooxygenase 2 inhibitor failed to demonstrate an inhibitory effect of IL1-ß on human isolated bronchi responsiveness to bradikinin. The inhibition of indomethacin on the relaxation of human control bronchi in response to bradykinin in the presence of thromboxane receptor antagonist is not modified by IL1-ß pre-treatment. Similar results were found on airway smooth muscle cell responsiveness to substance P. Substance P induced contraction was also mediated by thromboxane receptor stimulation, but on the oppposite, cyclooxygenase 2 inhibitor inhibit the IL1-ß induced potentiation of the substance P effect. Same experiments were performed with neurokinin A, but with slightly effect of IL1-ß on the smooth muscle cell responsiveness. In conclusion, it seems that IL1-ß potentiate the effect of bradykinin or tachykinin receptor agonist on the human isolated bronchi. The mechanism might involve regulation of thromboxane synthesis and cyclooxygenase synthesis.


Discussion

Mr Nijkamp insit on the importance of the bradykinin's role on the activation of airway smooth muscle cell. He said that induction of a treatment may enhance bronchi responsiveness to bradykinin and so it is possible to induce relaxation of smooth cell.

Mr Rabe ask about the range of variation responsiveness to bradykinin with IL1-ß and substance P.

Mr Olivieri wanted to know if influence of LPS and IL1-ß on smooth muscle cell have been measured only at 1 and 6 hours of incubation.
Mr Molimard answered that he measured the effect of LPS and IL1-ß at every hours of incubation but in his presentation he only presented the main results.

J.M. Tunon de Lara spoke about the IgE passive sensitization of human isolated bronchi and lung mast cells.

Passive sensitization of human isolated airways with serum from allergic asthmatic patients provides a good opportunity to study the role of IgE in bronchial reactivity. This serum with high concentration of IgE induce hyperresponsiveness of human isolated smooth cell in the airways. This passive sensitization is mainly related to mast cells bearing IgE molecule in differents smooth muscle layers. Derived products of the mast cells such as tryptase could enhance the contractile response of human isolated airways to non specific agonists such as histamine, KCl and tachynin. This effect is inhibited by the tryptase inhibitor benzamidine. Mast cell-derived products could contribute to sentitisation-induced hyperresponsiveness.


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Date de création: 12 Février 1998 -Dernière mise à jour: 23/07/98

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