Les filaments perlés : structure, fonctions et maladies associées.

Abstract

Les filaments perlés, ou microfibrilles riches en fibrilline, représentent l’un des principaux constituants du tissu conjonctif impliqué dans l’élasticité tissulaire. Cet élément structural est, soit associé à l’élastine amorphe (peau, ligaments…), soit présent comme tel dans certains tissus (peau, zonule…). L’analyse des différents composants des microfibrilles ainsi que la description des interactions susceptibles de s’établir avec les autres éléments de la matrice conjonctive ont permis d’envisager leur rôle majeur dans le maintien de l’intégrité tissulaire. Cependant, c’est l’étude du syndrome de Marfan, maladie génétique liée au gène de fibrilline-1, qui a irréversiblement révélé l’importance de ces microfibrilles dans la structuration tissulaire. De plus, des données récentes mettent en évidence l’implication des composants microfibrillaires autres que la fibrilline dans de nouvelles maladies.

Elastic fibers are extracellular amorphous aggregates which provide elasticity to numerous organs, and which can vary in size and arrangement depending on biomechanical requirements. All elastic fibers are characterized by a more or less important amorphous core of cross-linked elastin surrounded by a peripheral mantle of microfibrils. With a diameter of 10-12nm and average axial periodicity of 55 nm, microfibrils are also found in non-elastic tissues. In elastic tissues, they are thought to act as an organizing scaffold upon which tropoelastin is subsequently deposited. In non-elastic tissues, microfibrils may act as an anchoring structure between epithelia and their surrounding matrix or between adjacent epithelia. In addition to ultrastructural descriptive studies, increasing knowledge is available concerning microfibril composition. Based on biochemical and immuno-chemichal data, several microfibrillar proteins have been identified. At least three groups of proteins are believed to contribute to microfibrillar architecture: fibrillin, MAGP (microfibril associated glycoProtein) and LTBP (latent transforming growth factor-[beta] binding protein). Fibrillins 1 and 2 are known to be the major components of microfibrils; MAGP-1 and LTBP-1 also appear to be microfibril components, whereas MAGP-2 and LTBP-2 have been found to be either co-localized or poorly associated with microfibrils. The importance of the 350 kDa proteins, fibrillins, has been underlined by mutations in the genes coding for fibrillin-1 and fibrillin-2 which have been correlated with two major connective tissue diseases, Marfan syndrome (MFS) and Beals syndrome also named Congenital Contractural Arachnodactyly (CCA). Consequently, many fibrillar functions have emerged. For example, besides their ability to guide elastogenesis, fibrillin microfibrils appear to link elastic fibers both to each other and to other extracellular matrix components. Anchoring the cells to the matrix, they can also influence cellular behaviour. Furthermore, they are able, like collagen VI microfibrils, to modulate the platelet response to blood vessel injury.