A trypsin sensitive stromelysin isolated from rheumatoid synovial fluid is an activator for matrix metalloproteinases.
The processing of synovial fluids of patients suffering from rheumatoid arthritis led to the characterization of a neutral metalloproteinase with polymorphonuclear leukocyte progelatinase and polymorphonuclear leukocyte procollagenase activating properties. The activator exhibits a relative molecular mass of M(r) 27,000 and is an active form of stromelysin. Thus, it reacts specifically with antibodies raised against human stromelysin, splits polymorphonuclear leukocyte progelatinase in a manner characteristic of stromelysin, and is inhibited by EDTA as well as by a tissue inhibitor of metalloproteinases (TIMP-2). The activator shows a high specificity for the matrix metalloproteinases, polymorphonuclear leukocyte progelatinase and polymorphonuclear leukocyte procollagenase. It shows only weak hydrolysis of casein and gelatin, and it does not activate fibroblast M(r) 72,000 progelatinase. Brief treatment with trypsin does not lead to a significant change in the activator's relative molecular mass, but induces a rapid loss of its activating activity for polymorphonuclear leukocyte progelatinase, while its proteolytic activity against the synthetic substrate, N-(2,4)-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg, is increased about 3-fold. The same tryptic treatment does not affect the activator's proteolytic activity towards casein and gelatin.
Kolkenbrock
H
H
Deutsches Rheuma-Forschungszentrum Berlin, AG Biochemie, Germany.
Hecker-Kia
A
A
Orgel
D
D
Buchlow
G
G
Sörensen
H
H
Hauer
W
W
Ulbrich
N
N
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D017364:Collagenases / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000187:drug effects / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology; D018093:Gelatinases / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000187:drug effects* / Q000494:pharmacology* / Q000502:physiology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology; D013379:Substrate Specificity; D013582:Synovial Fluid / Q000201:enzymology* / Q000502:physiology; D014357:Trypsin / Q000494:pharmacology*
D004792:Enzyme Precursors; D016326:Extracellular Matrix Proteins; D004492:Edetic Acid; D014357:Trypsin; D005341:Fibrinolysin; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C022440:procollagenase; C069860:progelatinase; D019278:Matrix Metalloproteinase 3