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Characterization of a plasminogen activator produced by Acanthamoeba castellanii.

Abstract
Serine proteases play an important role in a diverse array of biological processes, including embryogenesis, metastasis, angiogenesis, thrombolysis and tissue invasion by certain parasites. The latter observation prompted us to explore the possibility that the tissue-invasive ocular parasite Acanthamoeba castellanii elaborates one or more serine proteases. Acanthamoeba sp. are pathogenic free-living amoebae that can produce an invasive, blinding inflammatory disease of the cornea, termed Acanthamoeba keratitis. The present study reports the preliminary purification and characterization of a novel plasminogen activator from an ocular isolate of A. castellanii. The parasite-derived enzyme has a molecular mass of approx. 40 kDa and produces a single band of lysis on fibrinogen-agarose zymographs. Activity of the enzyme is completely inhibited by treatment with diisopropylfluorophosphate, indicating that it is a serine protease. The parasite-derived serine protease is not inhibited by amiloride which is a strong inhibitor of urokinase-type plasminogen activator. Additionally, the enzyme is not inhibited by plasminogen activator inhibitor-1 which is the primary physiological inhibitor of both urokinase and tissue-type plasminogen activator. It does not cross-react with antibodies specific for human urokinase or tissue-type plasminogen activator. The parasite-derived enzyme activates plasminogen from several mammalian species, including human, cow and pig. Thus, it is possible that this parasite-derived serine protease contributes to the pathogenesis of Acanthamoeba keratitis.
AuthorsM M Mitra, H Alizadeh, R D Gerard, J Y Niederkorn
JournalMolecular and biochemical parasitology (Mol Biochem Parasitol) Vol. 73 Issue 1-2 Pg. 157-64 (Jul 1995) ISSN: 0166-6851 [Print] Netherlands
PMID8577323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Plasminogen Activator Inhibitor 1
  • Plasminogen Inactivators
  • Serine Proteinase Inhibitors
  • Isoflurophate
  • Amiloride
  • Plasminogen Activators
Topics
  • Acanthamoeba (enzymology, isolation & purification, pathogenicity)
  • Acanthamoeba Keratitis (parasitology)
  • Amiloride (pharmacology)
  • Animals
  • Cattle
  • Cross Reactions
  • Humans
  • Isoflurophate (pharmacology)
  • Molecular Weight
  • Plasminogen Activator Inhibitor 1 (pharmacology)
  • Plasminogen Activators (immunology, isolation & purification, metabolism)
  • Plasminogen Inactivators (pharmacology)
  • Serine Proteinase Inhibitors (pharmacology)

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