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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 & Dhome Laboratory February 13-14th 1998 in Montpellier- France (see programm, abstracts and experts comments ) Synthèse de la conférence sur la thématique Réparation bronchique Chantal Lafuma Samedi 14 Février 1998 Présentateurs Modérateurs Experts 11h00-12h00 Réparation bronchique Bronchial remodelling C. Lafuma (Paris) G. Mautino (Montpellier) Discussion 15' 15' 30' J. Bousquet (Montpellier) D. Olivieri (Parme, I) J. Shute (Southampton, UK) L. Fabbri (Ferrara, I) The airway epithelium may be injuried by inhaled allergens, toxic or infectious agents, or pollutants, leading to the airway damage, inflammation and subsequent shedding of the bronchial epithelial cells. The actual current concept is that wound-repair process following epithelial denudation is achieved by a predictable sequence of resting epithelial cell spreading, migration and proliferation (Zahm et al, 1997). Thus, cell-cell interaction via intercellar junctions and adhesion molecules, cell-matrix interaction via integrins, and matrix remodeling via matrix metalloproteinases (MMPs) contribute to the wound repair process of the respiratory epithelium, by mediating a cycle of attachment and detachment of cells from the underlying matrix substratum.

As regards cell/matrix interactions, fibronectin and its a5ß1-integrin receptor are particularly involved in the airway wound-repair process (Hérard et col, 1996), and subjected to positive regulation by epithelial growth factor (Wang et al, 1996).

As regards extracellular matrix remodeling, 92 kDa type IV collagenase (gelatinase B or MMP-9) is up-regulated and activated in airway epithelial cells involved in the repair process (Buisson et al, 1996).

During acute attack of asthma caracterized by massive neutrophils influx in airway bronchial spaces (Lamblin et al. 1998), we evidenced an acute release and/or production of 92 kDa gelatinase in bronchial lavage fluids when compared to discrete or moderate asthma, resulting in umbalance between the gelatinase and its inhibitor TIMP-1. High and significant correlation with the severity degree of bronchial epithelial cell shedding allowed us to propose that the acute 92 kDa gelatinase release may facilitate cell/basement membrane rupture via desmosome degradation, and/or contribute to the active repair process of damaged bronchial epithelium.

Such hypothesis is largely supported by above reported works and by our recent studies demonstrating:

• -i) the capacity of human bronchial epithelial cells in primary cultures to overexpress, both at the protein and mRNA level, the major 92 kDa gelatinase in response to LPS exposure or to pro-inflammatory cytokines such as IL-1ß and TNFa, without any TIMP-1 upregulation (Yao et al, 1996 and 1997)
• -ii) the modulation of this 92 kDa gelatinase overexpression by cell-matrix interactions (Yao et al, 1998)

. Asmanet ENFUMOSA Congrès Conçue et réalisée par: Michel Godard (at) Top
Date de création: 5 Décembre 1997-Dernière mise à jour: 23/07/98
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