Elastase secreted by activated polymorphonuclear leucocytes causes chondrocyte damage and matrix degradation in intact articular cartilage: escape from inactivation by alpha-1-proteinase inhibitor

Br J Exp Pathol. 1987 Feb;68(1):81-8.

Abstract

Anatomically intact, murine patellar cartilage was exposed to human polymorphonuclear leucocytes (PMN) stimulated with formyl-methionyl-leucyl-phenylalanine or Ca-ionophore A-23187. This resulted in an inhibition of chondrocyte proteoglycan synthesis and breakdown of cartilage matrix proteoglycans as shown with 35S-incorporation and autoradiography. These effects could not be inhibited by catalase or superoxide dismutase. A serine protease inhibitor and a specific elastase inhibitor prevented both proteoglycan degradation and chondrocyte damage, indicating that PMN-elastase is the causative agent. It was shown that elastase shed by PMN in close contact with the articular cartilage, can escape from complexing with alpha-1 proteinase inhibitor. We would hypothesize that the elastase owing to its dual action (matrix breakdown and inhibition of chondrocyte metabolism) is a major contributor to enzymatic cartilage destruction in inflammatory disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Proteins / pharmacology*
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / enzymology*
  • Organ Culture Techniques
  • Pancreatic Elastase / pharmacology*
  • Protease Inhibitors / pharmacology*
  • Proteoglycans / metabolism
  • alpha 1-Antitrypsin

Substances

  • Blood Proteins
  • Protease Inhibitors
  • Proteoglycans
  • alpha 1-Antitrypsin
  • Pancreatic Elastase