Amelioration of immune complex-mediated glomerulonephritis by synthetic protease inhibitors

• Published in: The American journal of pathology Vol. 127; no. 3; pp. 499 - 506
• Main Authors: Jennette, JC, Tidwell, RR, Geratz, JD, Bing, DH, Falk, RJ
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01-06-1987; American Society for Investigative Pathology
• Subjects: Amidines - therapeutic use; Animals; Benzimidazoles - therapeutic use; Biological and medical sciences; Complement Inactivator Proteins - therapeutic use; Creatinine - blood; Glomerulonephritis - therapy; Hydroxamic Acids - therapeutic use; Immune Complex Diseases - therapy; Indoles - therapeutic use; Male; Medical sciences; Mice; Pharmacology. Drug treatments; Protease Inhibitors - therapeutic use; Time Factors; Trypsin Inhibitors - therapeutic use; Urinary system; Glomerulonephritis; Immunopathology; Vertebrata; Chemotherapy; Mammalia; Urinary system disease; Mouse; Animal; Proteinase; Rodentia; Enzyme inhibitor; Immune complex
• ISSN: 0002-9440; 1525-2191

Proteases are involved in the pathogenesis of inflammatory diseases by participating in the activation of mediator systems and by producing proteolytic tissue injury. Homeostatic control of inflammation is accomplished in part by physiologic protease inhibitors. The authors investigated the effectiveness of a number of synthetic protease inhibitors in ameliorating the glomerular injury induced by immune complex-mediated glomerulonephritis in mice. Two amidine-type protease inhibitors, bis (5-amidino-2-benzimidazolyl)methane and 1,2-bis (5-amidino-2-benzimidazolyl)ethane, had the greatest effects. They caused a marked reduction in glomerular necrosis (P less than 0.001) but did not affect the amount or site of immune complex localization or leukocyte influx. The inhibition constants of the protease inhibitors against nine purified physiologic proteases were determined. These results were discussed in relation to the effectiveness of the protease inhibitors in reducing glomerular injury. This investigation indicates that the administration of synthetic protease inhibitors can have a beneficial effect on immune-mediated inflammatory injury.