title: Cleavage of recombinant murine interferon-gamma by plasmin and miniplasmin.
abstract: Plasmin reacted readily with recombinant murine interferon-gamma (rIFN-gamma) in vitro, reducing the relative molecular mass of each monomer by approximately 1,000. The amino terminus of the rIFN-gamma remained intact and no sites of internal peptide bond hydrolysis were detected, indicating that the plasmin target region is most likely near the carboxyl terminus. Cleavage of rIFN-gamma was observed with similar concentrations of trypsin or min-plasmin. By contrast, human neutrophil elastase failed to alter the structure of rIFN-gamma. The plasma proteinase inhibitor, alpha 2-antiplasmin, protected rIFN-gamma from plasmin digestion. Purified alpha 2-macroglobulin-plasmin complex cleaved rIFN-gamma; however, the activity was greatly reduced compared with the free proteinase. The antiviral activity of the rIFN-gamma was enhanced four- to fivefold by treatment with plasmin or trypsin. By contrast, naturally occurring murine IFN-gamma was inactivated by plasmin (80%), suggesting that the effect of plasmin on IFN activity can vary depending on the preparation studied. The importance of plasmin at the site of an immune reaction is well established. This investigation identifies plasmin and miniplasmin as physiologic proteinases capable of reacting with IFN-gamma in vivo.
authors.affiliation: Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
authors.forename: S L
authors.initials: SL
authors.lastname: Gonias
authors.forename: W W
authors.initials: WW
authors.lastname: Young
authors.forename: J W
authors.initials: JW
authors.lastname: Fox
mesh_terms: D000818:Animals; D004586:Electrophoresis; D005341:Fibrinolysin / Q000378:metabolism* / Q000502:physiology; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism* / Q000502:physiology; D011994:Recombinant Proteins
chemical_list: D010446:Peptide Fragments; D011994:Recombinant Proteins; C019493:miniplasmin; D007371:Interferon-gamma; D005341:Fibrinolysin