title: Does human leukocyte elastase degrade intact skin elastin?
abstract: This study aimed to investigate the susceptibility of intact fibrillar human elastin to human leukocyte elastase and cathepsin G. Elastin is a vital protein of the extracellular matrix of vertebrates, and provides exceptional properties including elasticity and tensile strength to many tissues and organs, including the aorta, lung, cartilage, elastic ligaments and skin, and is thus critical for their long-term function. Mature elastin is an insoluble and extremely durable protein that undergoes very little turnover, but sustained exposure to proteases may lead to irreversible and severe damage, and thus to functional loss of the elastic fiber network. Hence, it is a key issue to understand which enzymes actually initiate elastolysis under certain pathological conditions or during intrinsic aging. In this paper, we provide a complete workflow for isolation of pure and intact elastin from very small tissue samples to test enzymes for their elastolytic potential. This workflow was applied to skin samples from variously aged individuals, and it was found that strong differences exist in the degradability of the elastins investigated. In summary, human leukocyte elastase was unable to degrade intact elastin fibers but hydrolyzed elastin derived from the skin of old people. However, cathepsin G cleaved all elastin samples, even those derived from younger individuals. These results indicate that human leukocyte elastase is not a driving force for elastolysis, but may nevertheless promote further breakdown of elastic fibers after the action of other enzymes such as cathepsin G.
authors.affiliation: Institute of Pharmacy, Faculty of Natural Sciences I, Martin Luther University Halle-Wittenberg, Germany. schmelzer@pharmazie.uni-halle.de
authors.forename: Christian E H
authors.initials: CE
authors.lastname: Schmelzer
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jung
authors.forename: Johannes
authors.initials: J
authors.lastname: Wohlrab
authors.forename: Reinhard H H
authors.initials: RH
authors.lastname: Neubert
authors.forename: Andrea
authors.initials: A
authors.lastname: Heinz
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D056649:Cathepsin G / Q000378:metabolism*; D002648:Child; D004549:Elastin / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D012867:Skin / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D004549:Elastin; D056649:Cathepsin G; D019272:Leukocyte Elastase