Treatment of Inflammmation by Purified Human Proteinase Inhibitor.

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Inhibitory activity of plasma on thermolysin, a bacterial proteinase inhibitor, was significantly higher in patients with Idiopathic Nephrotic Syndrome (INS) at relapse than in those in remission, chance proteinuria and/or hematuria and control subjecets. Sephadex G-200 gel-chromatography of plasma revealed the thermolysin inhibitory activity confined in the large molecular fractions, and Sephacryl S-300 chromatography, performed to purify alpha2-macroglobulin ( alpha2-MU) from human plasma, demonstrated the coincidence of the thermolysin inhibitory acitivity with alpha2-MU. These results suggest that the increased thermolysin ihnibitory activity of nephrotic plasma alpha2-MU contributes as a defense against possible invasion pathogens by inactivating proteinases elaborated by these organisms.alpha2-MU was examined for deposition in kidney tissue, using FITC-labelled anti-human alpha2-MU antibody (goat). A four-year-old male, exhibiting steroid refractory nephrotic syndrome, was found … More to have diffuse deposition of alpha2-MU in the glomeruli which showed diffuse mesangial proliferation and partial hyalinizati on by light microscopy. Administration of Camostat mesillate, a commercially available synthetic proteinase inhibitor, was started and he responded well to the therapy. Granular deposition of alpha2-MU was demonstrated in the mesangium of mice after the intraperitoneal injection of alpha2-MU. The deposition of alpha2-MU in the glomeruli may directly suggest the participation of proteinase (s) and proteinase inhibitor (s) in the inflammatory processes.In INS, proteinase inhibitory activity was significantly decreased when calculated per one mole of alpha2-MU, implicating a reduced proteinase inhibiting capacity of alpha2MU. The decreased proteinase inhibiting capacity of alpha2-MU was significantly associated with the inhibitory activity of plas ma on normal lymphocyte blastogenesis. Purified alpha2-MU complexed with chymotrypsin, intensively inhibited normal lymphocyte blastogenesis, induced by Concanavalin A, as compared to free alpha2-MU. Vascular permeability induced by nephrotic plasma was slightly ameliorated by the administration of purified alpha2-MU. Less