Open AccessProteolytic inactivation of α 1 ‐antitrypsin and α 1 ‐antichymotrypsin by neutrophils in arthritic joints
Author(s) -
Abbink Jannie J.,
Kamp Angela M.,
Nuijens Jan H.,
Swaak Tom J. G.,
Hack C. Erik
Publication year - 1993
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780360206
Subject(s) - alpha (finance) , elastase , synovial fluid , pancreatic elastase , arthritis , chemistry , neutrophil elastase , osteoarthritis , microbiology and biotechnology , antibody , inflammation , medicine , immunology , enzyme , biochemistry , biology , pathology , construct validity , nursing , alternative medicine , patient satisfaction
Objective. In vitro, activated neutrophils create a microenvironment in which proteinase inhibitors are inactivated through the coordinate action of reactive oxygen species and released elastase. We investigated whether such a mechanism may contribute to the destruction of the joint tissues in arthritis. Methods. We analyzed the state of α 1 ‐antitrypsin (α 1 AT) and α 1 ‐antichymotrypsin (α 1 ACT), the two major inhibitors of the neutrophilic serine proteinases, in synovial fluid (SF) from patients with inflammatory arthropathies (n = 71) and osteoarthritis (OA) (n = 11), and related the results to neutrophil activation in SF. Results. The ratio of functional to antigenic levels of α 1 AT in SF of patients with inflammatory joint diseases was similar to that of α 1 AT in normal plasma, whereas that of α 1 ACT was significantly decreased. Patients with inflammatory arthropathies had significantly higher levels of inactivated α 1 AT (iα 1 AT) and inactivated α 1 ACT (iα 1 ACT) in SF (as determined with monoclonal antibodies specific for the inactivated [i.e., proteolytically inactivated and/or complexed] forms of these inhibitors) than patients with OA ( P < 0.005). Inactivated α 1 AT and iα 1 ACT levels corresponded to 0.3–11% and 3–99%, respectively, of the total amount of these inhibitors in SF. Most of the iα 1 AT in SF had a lower M r than that of native α 1 AT. Inactivated α 1 ACT in SF had an M r identical to that of nonfunctional α 1 ACT in plasma treated with chymotrypsin. Levels of both iα 1 AT and iα 1 ACT correlated significantly with lactoferrin and elastase levels. Conclusion. These results suggest that α 1 AT and α 1 ACT in arthritic joints are inactivated in part by activated neutrophils, suggesting a role for these cells in impairment of the local balance between proteinases and their inhibitors in arthritis.