Collagenase in synovitis of rheumatoid arthritis.
There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.
Sorsa
T
T
Department of Anatomy, Helsinki University, Finland.
Konttinen
Y T
YT
Lindy
O
O
Ritchlin
C
C
Saari
H
H
Suomalainen
K
K
Eklund
K K
KK
Santavirta
S
S
D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D017364:Collagenases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D020784:Matrix Metalloproteinase 8; D009504:Neutrophils / Q000201:enzymology; D013583:Synovial Membrane / Q000201:enzymology; D013585:Synovitis / Q000201:enzymology*
D017364:Collagenases; D020784:Matrix Metalloproteinase 8