Elastin Production and Degradation in Cutis Laxa Acquisita

• Published in: Journal of investigative dermatology Vol. 103; no. 4; pp. 583 - 588
• Main Authors: Fornieri, Claudio, Quaglino, Daniela, Lungarella, Giuseppe, Cavarra, Eleonora, Tiozzo, Roberta, Giro, Maria Gabriella, Canciani, Mario, Davidson, Jeffrey M, Ronchetti, Ivonne Pasquali
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.1994
• Subjects: Adult; Biopsy; cathepsin G; Cells, Cultured; Child, Preschool; Chromatography, High Pressure Liquid; Cutis Laxa - metabolism; Elastin - metabolism; Enzyme Inhibitors - blood; Enzyme-Linked Immunosorbent Assay; Fibroblasts - metabolism; Fibroblasts - ultrastructure; Humans; in vitro; lung; Male; Pancreatic Elastase - antagonists & inhibitors; Pancreatic Elastase - blood; proteases; skin; Skin - pathology; Tropoelastin - metabolism; lung; skin; cathepsin G; in vitro; proteases
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12396893

A case of cutis laxa acquisita was studied with the aim of defining the molecular defects involved and comparing them with those of an inherited form of cutis laxa. In the acquisita form of cutis laxa ultrastructural and biochemical observations confirmed a dramatic reduction of dermal elastin, whereas collagen content was normal. Elastin mRNA expression as well as tropoelastin production by dermal fibroblasts, in vitro, were normal compared with control cells, as revealed by in situ hybridization and enzyme-linked immunosorbent assay, respectively. Lysyl oxidase activity, measured on cultured fibroblasts, was reduced to 60% compared with age-matched control subjects. Unlike control skin fibroblasts or fibroblasts from inherited cutis laxa, the affected skin cells from cutis laxa acquisita predominantly expressed an elastolytic activity identified as cathepsin G. Patient serum also has reduced elastase inhibitory capacity and reduced levels of α1-antiproteinase inhibitor (α1-antitrypsin). Although cutis laxa acquisita is a heterogeneous group of disorders, findings in this patient were consistent with excessive loss of cutaneous elastin due to the combined effects of several factors, such as low lysyl oxidase activity together with high levels of cathepsin G and reduction of circulating proteinase inhibitor(s).