title: Cell death by apoptosis is a feature of the rheumatoid nodule.
abstract: OBJECTIVE
  To examine the site and extent of apoptosis in the rheumatoid nodule and to determine whether this process make a significant contribution to the control of inflammation in the rheumatoid nodule as in other granulomas.
  
  
  METHODS
  Nine nodules and seven synovial membranes were examined by terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) in situ and a subset was further examined by DNA electrophoresis. The phenotype of apoptotic cells was identified using monoclonal antibodies and immunohistology.
  
  
  RESULTS
  Apoptosis occurred in all zones of the nodule and, except in one case, was not focused adjacent to the necrotic centre. Apoptosis occurred in 3.5 (4.5)% (mean (SD)) of cells in the nodule and 3.6 (3.1)% of cells in synovial membranes. Apoptosis was more common in nodule T cells (4.1 (2.9)%) than fibroblasts (1.0 (1.4)%), p = 0.01. Among macrophages 3.2 (4.7)% were apoptotic. Banding of DNA consistent with apoptosis was seen in two of three nodules examined.
  
  
  CONCLUSIONS
  Apoptosis occurs at a low level in the nodule, similar to the synovial membrane. The results suggest that two modes of cell death occur in the nodule: apoptosis, which occurs throughout the nodule; and necrosis, which is concentrated near the necrotic centre. Apoptosis was more common in infiltrating inflammatory cells than in resident fibroblasts. These results are consistent with the proposal that apoptosis of infiltrating inflammatory cells is important in controlling accumulation of cells in the rheumatoid nodule as has been established in experimental granulomas.
authors.affiliation: Department of Medical and Surgical Sciences, Dunedin School of Medicine, PO Box 913, Dunedin, New Zealand. john.highton@stonebow.otago.sc.nz
authors.forename: J
authors.initials: J
authors.lastname: Highton
authors.forename: P A
authors.initials: PA
authors.lastname: Hessian
authors.forename: A
authors.initials: A
authors.lastname: Kean
authors.forename: M
authors.initials: M
authors.lastname: Chin
mesh_terms: D000328:Adult; D017209:Apoptosis; D002452:Cell Count; D004247:DNA / Q000032:analysis; D004587:Electrophoresis, Agar Gel; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012218:Rheumatoid Nodule / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D004247:DNA; D008727:Methotrexate