1. Academic Validation
  2. Novel inhibitors of polymorphonuclear neutrophil (PMN) elastase and cathepsin G: evaluation in vitro of their potential for the treatment of inflammatory connective tissue damage

Novel inhibitors of polymorphonuclear neutrophil (PMN) elastase and cathepsin G: evaluation in vitro of their potential for the treatment of inflammatory connective tissue damage

  • Int J Immunopharmacol. 1990;12(7):787-95. doi: 10.1016/0192-0561(90)90043-m.
N S Doherty 1 R J Dinerstein S Mehdi
Affiliations

Affiliation

  • 1 Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Abstract

Inhibitors of neutrophil proteases may have therapeutic effects in inflammatory diseases. MDL 27,324 (Dansyl-Ala-Ala-Pro-Val-CF3), inhibits human neutrophil Elastase and MDL 27,399 (MeOSucc-Ala-Ala-Pro-Phe-COOCH3), inhibits human neutrophil Cathepsin G. These compounds individually or in combination, partially inhibited the hydrolysis of fluoresceinated bovine serum albumin and fluoresceinated immune complexes by rat and human neutrophil granule lysate. In contrast, the combination of inhibitors completely prevented the breakdown of a complex connective tissue substrate, azure hide powder. Rat neutrophils phagocytosed and hydrolyzed fluoresceinated immune complexes, a process which was inhibited by cytochalasin B (15 micrograms/ml, 65% inhibition) and chloroquine (200 microM, 80% inhibition). Although MDL 27,324 was taken up by the cells, it had only a modest inhibitory effect on the proteolysis of ingested fluoresceinated immune complexes (200 microM, 20% inhibition); MDL 27,399 had similar limited efficacy. Therefore, these compounds may be effective inhibitors of neutrophil serine proteases secreted into the extracellular space during inflammation without interfering with the normal process of intracellular degradation of phagocytosed material.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-126822
    中性粒细胞蛋白酶抑制剂