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 proteoglycanases. In vitro evaluation was done using bovine nasal septum aggrecan and aggrecan/hyaluronan aggregate as substrates. Enzyme activity was assessed by the ability of the proteinases to abrogate the ability of aggrecan to aggregate with hyaluronan. In vivo activity of the proteinases was tested by injecting purified HLE and HCG intra-articularly into rabbit stifle joints and quantifying the levels of proteoglycan released into synovial fluids. On a molar basis, HCG was at least tenfold more potent than HLE as a proteoglycanase in vitro. Moreover, HCG was twofold more potent as a proteoglycanase in vivo. In contrast, HLE hydrolyzed elastin approximately 22-fold faster than HCG, but was only slightly more rapid than HCG when [3H]-transferrin was used as substrate. These data indicate that HCG is more potent than HLE as a proteoglycanase both in vitro and in vivo. Thus, HCG could be more important in the pathogenesis of rheumatoid arthritis than previously suspected.
McDonnell
J
J
Merck Research Laboratories, Rahway, New Jersey 07065.
Lobner
J M
JM
Knight
W B
WB
Lark
M W
MW
Green
B
B
Poe
M
M
Moore
V L
VL
D053674:Aggrecans; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology; D002358:Cartilage, Articular / Q000378:metabolism; D056649:Cathepsin G; D002403:Cathepsins / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D002417:Cattle; D004549:Elastin / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007269:Injections, Intra-Arterial; D037181:Lectins, C-Type; D019272:Leukocyte Elastase; D010196:Pancreatic Elastase / Q000008:administration & dosage / Q000494:pharmacology*; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D012697:Serine Endopeptidases; D013582:Synovial Fluid / Q000737:chemistry; D014162:Transfection; D014316:Tritium
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D014316:Tritium; D006820:Hyaluronic Acid; D004549:Elastin; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase