Collagenase reserves in polymorphonuclear neutrophil leukocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis.
Degradation of cartilage in rheumatoid arthritis (RA) may be in part due to release of collagenase from specific granules of polymorphonuclear neutrophil leukocytes (PMNs) during degranulation. We decided to study, not synovial fluid (SF) collagenase, but PMN collagenase reserves. PMN were isolated from parallel SF and peripheral blood (PB) samples obtained from 7-arthritis patients. PMNs were stimulated in vitro by tetradecanoyl-phorbol-13-acetate (TPA). Collagenase activity in the supernatant without and with phenylmercuric chloride activation was studied. Compared to PB PMNs, there was no consistent decrease in the total collagenase reserves in the inflammatory SF PMNs. This suggests that the release of collagenase in the inflammatory synovial fluid does not deplete SF PMNs of the collagenase synthesized at the myelocyte stage. The role of PMN collagenase in pathogenesis of cartilage destruction would then seem to be more dependent on local release and autoactivation at cartilage surface by adherent PMNs and not excessive collagenase release from free floating SF PMNs at single cell level. Furthermore, under the experimental conditions used the proportion of collagenase released in active form was higher in SF PMN specimens than in PB PMN specimens (p less than 0.01). The predominant collagenous component of adult cartilage, native type II collagen, was degraded by PMN collagenase as fast as native type I collagen. These findings suggest an important role for this enzyme in destruction of the free cartilage surface in RA.
Konttinen
Y T
YT
Institute of Molecular Immunology, Hospital for Joint Disease, NYU Medical School, New York.
Lindy
O
O
Kemppinen
P
P
Saari
H
H
Suomalainen
K
K
Vauhkonen
M
M
Lindy
S
S
Sorsa
T
T
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D001773:Blood Cells / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism; D006801:Humans; D003012:Microbial Collagenase / Q000032:analysis*; D009504:Neutrophils / Q000737:chemistry*; D013582:Synovial Fluid / Q000166:cytology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D003094:Collagen; D003012:Microbial Collagenase; D013755:Tetradecanoylphorbol Acetate