Degradation in vivo of articular cartilage in rheumatoid arthritis and juvenile chronic arthritis by cathepsin G and elastase from polymorphonuclear leukocytes

Abstract

Peroxidase-anti-peroxidase (PAP) staining and specific antibodies against cathepsin G and elastase from polymorphonuclear leukocytes (PMN) were applied to pannus-free and microscopically intact superficial articular cartilage. Restricted local deposits containing cathepsin G and elastase were found in three of ten patients with seropositive rheumatoid arthritis (RA), in one of three patients with seronegative RA and in one patient with juvenile chronic arthritis (JCA). Similarly, localized deposits of IgG and C3 were found in the patients with seropositive RA and JCA, but not in the patient with seronegative RA. Adjacent sections exhibited esterase activity in and around the PMN. In proteinase-positive areas from patients with seropositive RA the inhibitors alpha 1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-MG) were present in two of three and one of three patients, respectively. In JCA only alpha 1-proteinase inhibitor was present, and in seronegative RA no inhibitors were found. No staining of articular cartilage was observed in a patient with psoriatic arthritis. One of three cases with osteoarthritis exhibited patchy superficial staining for IgG only. In articular cartilage covered by pannus, in three patients with seropositive RA, in one with seronegative RA and in the patient with JCA a few regions with variably dense PMN infiltrates were observed. Cathepsin G, elastase and esterase activity were found in and around the PMN. In one of the three patients with seropositive RA the adjacent cartilage-pannus junction exhibited distinct staining for cathepsin G and elastase, but not for IgG/C3 and proteinase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative study of tetranectin levels in serum and synovial fluid of patients with rheumatoid arthritis, seronegative spondylarthritis and osteoarthritis

“…Moreover, TN&I-AT and TN/~2-MG molar ratios correlated negatively with serum inflammatory markers in RA patients. It appears that although the proteinase inhibitors are produced in high concentrations in the affected joints, due to some negative feedback mechanism, they are unable to prevent cartilage destruction [35][36][37]. This could be due to the binding of elastase and cathepsin G to cartilage, which localises the activity of these proteinases and protects them from the action of cq-AT, c~ -MG and other inhibitors [35,36].…”

The cell biology of leukocyte-mediated proteolysis

“…HLE has also been shown to bind avidly to cartilage [119,120] and catalytically active HLE has been localized at the cartilage-panus junction of patients with rheumatoid arthritis [121]. Moreover, cartilage-bound enzyme has been shown to be catalytically active yet substantially resistant to inhibition by both ␣ 1 -proteinase inhibitor and ␣ 2 -macroglobulin in vitro [120,122].…”

Mechanisms of human neutrophil‐mediated cartilage damage in vitro: The role of lysosomal enzymes, hydrogen peroxide and hypochlorous acid

“…Neutrophils are numerous in the inflamed joint in the early stages of rheumatoid arthritis and during acute flare-ups of the disease (3). Neutrophils have been detnonstrated in eroded areas of cartilage, particularly at the cartilage-pannus junction (4)(5)(6) and have been implicated in cartilage injury (4,5). We have shown that human neutrophils can damage human articular cartiCorrespondence: Dr I. C. Kowanko.…”

“…The mechanism of this neutrophii-mediated damage is not well understood, but has been attributed largely to the lysosomal proteases, particularly elastase (5,(9)(10)(11)(12). Reactive oxygen metabolites produced during the respiratory burst may also be involved (13)(14)(15).…”