COMPARISON OF THE PROTEOGLYCANOLYTIC ACTIVITIES OF HUMAN-LEUKOCYTE ELASTASE AND HUMAN CATHEPSIN-G IN-VITRO AND IN-VIVO

In this study, we evaluated the in vitro and in vivo potency of human leukocyte elastase (HLE) and human cathepsin G (HCG) as proteoglycanas es. In vitro evaluation was done using bovine nasal septum aggrecan an d aggrecan/hyaluronan aggregate as substrates. Enzyme activity was ass essed by the ability of the proteinases to abrogate the ability of agg recan to aggregate with hyaluronan. In vivo activity of the proteinase s was tested by injecting purified HLE and HCG intra-articularly into rabbit stifle joints and quantifying the levels of proteoglycan releas ed into synovial fluids. On a molar basis, HCG was at least tenfold mo re potent than HLE as a proteoglycanase in vitro. Moreover, HCG was tw ofold more potent as a proteoglycanase in vivo. In contrast, HLE hydro lyzed elastin approximately 22-fold faster than HCG, but was only slig htly more rapid than HCG when [H-3]-transferrin was used as substrate. These data indicate that HCG is more potent than HLE as a proteoglyca nase both in vitro and in vivo. Thus, HCG could be more important in t he pathogenesis of rheumatoid arthritis than previously suspected.