Amelioration of immune complex-mediated glomerulonephritis by synthetic protease inhibitors

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 effectiv...

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Published inThe 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
LanguageEnglish
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
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Summary: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.
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ISSN:0002-9440
1525-2191