title: Catabolism of intact fibrillin microfibrils by neutrophil elastase, chymotrypsin and trypsin.
abstract: We present ultrastructural and biochemical evidence for the turnover of intact fibrillin microfibrils by the serine proteinases, neutrophil elastase, chymotrypsin and trypsin. Rotary shadowing electron microscopy revealed that serine proteinase treatment of intact microfibrils isolated from foetal bovine skin resulted in extensive degradation. Microfibrils were destroyed by neutrophil elastase and effectively disrupted by chymotrypsin and trypsin, with no morphologically identifiable arrays remaining. Evidence of defined fibrillin degradation products was obtained by Western blotting of these enzyme-treated fibrillin assemblies. Fibrillin immunoprecipitated from dermal fibroblast culture medium was also comprehensively degraded by these enzymes. These observations demonstrate that serine proteinases are potent effectors for the physiological and pathological catabolism of microfibrils, and suggest a key role in elastic fibre degradation.
authors.affiliation: School of Biological Sciences, University of Manchester, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Kielty
authors.forename: D E
authors.initials: DE
authors.lastname: Woolley
authors.forename: S P
authors.initials: SP
authors.lastname: Whittaker
authors.forename: C A
authors.initials: CA
authors.lastname: Shuttleworth
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002918:Chymotrypsin / Q000378:metabolism*; D003238:Connective Tissue / Q000378:metabolism / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D000071837:Fibrillins; D006801:Humans; D019272:Leukocyte Elastase; D008840:Microfilament Proteins / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism*; D012867:Skin / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D014357:Trypsin / Q000378:metabolism*
chemical_list: D000071837:Fibrillins; D008840:Microfilament Proteins; D002918:Chymotrypsin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D014357:Trypsin