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

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.