Analysis of the ex vivo specificity of human gelatinases A and B towards skin collagen and elastic fibers by computerized morphometry

Cutaneous aging and chronic exposure to UV irradiation leads to alterations in the appearance and biochemical composition of the skin. Members of the MMP family have been involved in the destruction of the extracellular matri x. Among them, gelatinases A and B were found to display elastolytic activi ty, in vitro. In this study, we first determined the ex vivo elastolytic po tential of both endopeptidases, using human skin tissue sections and comput erized morphometric analyses, and compared it with those of neutrophil elas tase. In such conditions, gelatinase B (50 nM) induced 50% elastolysis. The percentage of elastic fibers degraded by gelatinase A (10-100 nM) never ex ceeded 10%. Elastolysis by gelatinase B and leukocyte elastase was characte rized by a decrease in fiber length and an increase in the average diameter of the fibers.-In addition, gelatinase B exhibited fibrillin-degrading act ivities. On the contrary, gelatinase A (50 nM) elicited up to 50% hydrolysi s of collagen fibers, preferentially degrading type III collagen fibers. Ge latinase B did not promote any collagen degrading activity. Our data sugges ted that in vivo gelatinases could disrupt most extracellular matrix struct ures of human skin. Gelatinase B and to a much lesser extent, gelatinase A would degrade components of the elastic fibers network while gelatinase A, but not gelatinase B, would alter mostly collagen fibers and also degrade c onstituents of the dermo-epidermal junction. (C) 2000 Elsevier Science B.V. /International Society of Matrix Biology. All rights reserved.