SUBEPITHELIAL FIBROSIS AND DEGRADATION OF THE BRONCHIAL EXTRACELLULAR-MATRIX IN CYSTIC-FIBROSIS

Cystic fibrosis is a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator gene. Chronic inflammati on and proteolysis lead to progressive damage of the bronchial wall. E xtracellular matrix determines the structural organization and the mec hanical properties of lung airways. It was thus examined in nine patie nts with cystic fibrosis (six bronchial biopsies and three lobectomies ) in order to assess its level of alteration. The submucosal changes i n matrix protein distribution were analyzed by immunochemistry and ele ctron microscopy: the subepithelial basal lamina was thinned; an acell ular collagen fiber layer composed of interstitial collagens (types I and III) subtended by tenascin and devoid of elastin-associated microf ibrils was deposited beneath the basal lamina; this dense fibrous depo sit generally formed a thick layer and could extend into the bronchial wall; the bronchial elastic framework lost arborescent distribution a nd appeared slender, packed, or lacunar; ultrastructural observation g ave evidence for elastic and collagenic fiber lysis. Proteolytic activ ity is probably the major cause of matrix degradation. Fibrosis appear s as a repair process rather than as an active fibrogenesis. The rever sibility of extracellular matrix alterations is an important challenge and various interventions such as anti-inflammatory treatments can be targeted to halt or reverse this degradation process.