Cleavage of Recombinant Murine Interferon-7 by Plasmin and Miniplasmin

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Abstract
Plasmin reacted readily with recombinant murine interferon-γ(rIFN-γ) in vitro, reducing the relative molecular mass of each monomer by approximately 1,000. The amino terminus of the rIFN-γ 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-γ was observed with similar concentrations of trypsin or minplasmin. By contrast, human neutrophil elastase failed to alter the structure of rIFN-γ. The plasma proteinase inhibitor, α2-antiplasmin, protected rIFN-γ from plasmin digestion. Purified α2-macroglobulin-plasmin complex cleaved rIFN-γ; however, the activity was greatly reduced compared with the free proteinase. The antiviral activity of the rIFN-γ was enhanced four− to fivefold by treatment with plasmin or trypsin. By contrast, naturally occurring murine IFN-γ 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-γ in vivo.