title: Intraarticular alpha 2-macroglobulin complexes and proteolytic activity in children with juvenile rheumatoid arthritis.
abstract: In juvenile rheumatoid arthritis (JRA), it is likely that the release of proteolytic enzymes from activated synovial fluid neutrophils overwhelms the major protease inhibitor, alpha 2-macroglobulin (alpha 2-MG), and leads to cartilage destruction. Due to the unique nature of the alpha 2-MG-protease complex, proteolytic function is maintained until the complex is cleared. In this study, we sought to determine the concentration of alpha 2-MG-protease complexes in synovial fluid of patients with JRA, the proteolytic activity found in their synovial fluid, and whether the alpha 2-MG complexes are associated with increased proteolytic activity. The JRA patients' synovial fluids had complex levels of 217.0 +/- 192.2 nmol/L--significantly elevated compared with plasma values (p < 0.001) and with control synovial fluid (p < 0.05). Elastase activity (almost entirely neutrophil elastase) was detected in all JRA synovial fluid samples (mean 2.9 +/- 2.6 mg/L) and significantly correlated with alpha 2-MG-complex values (r = 0.67, p < 0.01). Synovial fluid tryptic activity was detectable in all JRA patients but did not significantly correlate with alpha 2-MG complexes (r = 0.53, p > 0.05). Seventy-four percent of total elastase activity and 41% of total tryptic activity were contained in the alpha 2-MG-complex fractions. We suggest that the increased concentration of synovial fluid alpha 2-MG complexes with retained elastase activity contributes to continued proteolysis and joint destruction and may affect the subsequent disease course through its role as a modulator of IL-6.
authors.affiliation: Division of Pediatric Gastroenterology and Nutrition, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
authors.forename: J J
authors.initials: JJ
authors.lastname: Levine
authors.forename: D D
authors.initials: DD
authors.lastname: Sherry
authors.forename: D K
authors.initials: DK
authors.lastname: Strickland
authors.forename: N T
authors.initials: NT
authors.lastname: Ilowite
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase; D008297:Male; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D000511:alpha-Macroglobulins; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D014357:Trypsin