title: Wound fluid from venous leg ulcers degrades plasminogen and reduces plasmin generation by keratinocytes.
abstract: Plasminogen, the pro-enzyme of plasmin, aids various processes essential for normal, acute wound healing, such as fibrinolysis and cell migration. We have investigated if plasminogen is available to perform these functions in chronic wounds such as venous leg ulcers. We report that plasminogen is degraded by fluid from venous leg ulcers to a number of fragments, including kringle domains 1-3, an angiostatin-related protein. The enzyme responsible was inhibited by the serine protease inhibitor phenyl-methylsulfonyl fluoride, but was not inhibited by alpha1-anti-trypsin, an inhibitor of neutrophil elastase, by alpha2-anti-plasmin, an inhibitor of plasmin, or by the matrix metalloprotease inhibitor 1,10 phenanthroline. Plasminogen degraded by wound fluid was a weaker substrate than intact plasminogen for plasmin generation by the keratinocyte cell line HaCaT. These results suggest that serine protease activity in leg ulcer fluid degrades plasminogen and support the hypothesis that keratinocyte migration may be impaired in leg ulcers because of a reduced availability of intact plasminogen for plasmin generation.
authors.affiliation: European Institute of Health and Medical Sciences, University of Surrey, Guildford, UK.
authors.forename: R
authors.initials: R
authors.lastname: Hoffman
authors.forename: S
authors.initials: S
authors.lastname: Starkey
authors.forename: J
authors.initials: J
authors.lastname: Coad
mesh_terms: D043168:Angiostatins; D005122:Exudates and Transudates / Q000201:enzymology / Q000502:physiology*; D005341:Fibrinolysin / Q000096:biosynthesis*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D014647:Varicose Ulcer / Q000503:physiopathology*; D014947:Wounds and Injuries / Q000201:enzymology / Q000503:physiopathology
chemical_list: D010446:Peptide Fragments; D011480:Protease Inhibitors; D043168:Angiostatins; D010958:Plasminogen; D019272:Leukocyte Elastase; D005341:Fibrinolysin