Elastase-like protease and elastolytic activities expressed in cultured dermal fibroblasts derived from lesional skin of patients with pseudoxanthoma elasticum, actinic elastosis, and cutis laxa

Abstract

Pseudoxanthoma elasticum (PXE), actinic elastosis, and cutis ‘laxa are three cutaneous disorders in which alterations in the structure of dermal elastic fibers are seen [1,2]. Elastic fibers in PXE are increased in number, appear clumped and become calcified. The acquired skin disorder, actinic elastosis, is described as a proliferation (elastosis) of abnormal elastic fibers that become thickened and tangled [3]. Cutis rhomboidalis nuchae represents an extensive form of actinic elastosis on the posterior aspect of the neck of individuals 60 years of age or older who have had chronic exposure to the sun. Cutis laxa is considered to be a more generalized elastolysis; the skin is abnormally lax and hangs in folds; histopathological changes include a reduction in elastic fibers. In addition, the remaining elastic fibers appear thin and fragmented. Therefore, these three distinct disorders are all characterized by abnormalities in elastic fibers. It has been suggested that proteolytic degradation by elastase(s) plays a role in the formation of the elastin abnormalities seen in disease states [4-61. These proteases have been found in extracts prepared from dermal fibroblasts [7-lo] and in sera from a patient with cutis laxa [ll]. In this investigation, fibroblast cultures were established from affected areas of patients with pseudoxanthoma elasticum, actinic elastosis (cutis rhomboidalis nuchae), and cutis laxa. Elastase-like protease and elastolytic activities were assayed using succinyl trialanine paranitroanilide (SANA) and radiolabeled insoluble skin elastin in extracts of these cells.