[Matrix metalloproteinase (MMP-9) in patients with rheumatoid arthritis].
MMP-9 degrades type IV collagen, gelatin, type V collagen, and type XI collagen. We measured proMMP-9 and proMMP-9/TIMP-1 complex in sera and joint fluids by sandwich ELISA, and examined immunohistochemically the expression of these proteins in joint tissue from patients with rheumatoid arthritis (RA). ProMMP-9 was purified by the three chromatographic steps from the culture medium of HT1080 cells. Purified proMMP-9 and activated MMP-9 by APMA showed a single band of Mr92000, Mr67000, resectively on gelatin-zymography. We raised two monoclonal antibody colones 2G9, 8G7 against proMMP-9 with BALB/c mice. 2G9 and 8G7 reacted with proMMP-9 on Western blotting, and these clones reacted proMMP-9 and proMMP-9/TIMP-1 complex on sandwich ELISA, specifically. ProMMP-9 concentration in 86 sera (749.4+/-940.2 ng/ml) and 54 joint fluids (4539.9+/-7681.5 ng/ml) from patients with RA was significantly higher than those of patients with osteoarthritis and control. Immunohistochemistry with 2G9 showed that in rheumatoid synovium proMMP-9 localized in neutrophils and monocytes diffusely infiltrated the sublining layer. In addition, osteoclasts in rheumatoid subchondral bone were intensively stained. ProMMP-9 concentration in joint fluids from 39 RA patients was not correlated to stage and class of Steinbrocker and to clinical laboratorial data. But, it was positively correlated to the number of proMMP-9 positive cells in RA synovium (r=0.607) and the score of Roony's diffuse infiltrates of lymphocytes (r=0.720). Our results suggest a role of MMP-9 in joint destraction of RA throughout neutrophils and monocytes, and a regulation of this enzyme by lymphocytes.
Seki
M
M
Department of Orthopaedic Surgery, School of Medicine, Tohoku University, Sendai-city.
Uzuki
M
M
Ohmoto
H
H
Yoshino
K
K
Maeda
S
S
Kokubun
S
S
Sakurai
M
M
Sawai
T
T
D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages; D008297:Male; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009504:Neutrophils; D013582:Synovial Fluid / Q000737:chemistry* / Q000166:cytology
D017364:Collagenases; D020780:Matrix Metalloproteinase 9