Expression of the apoptosis accelerator Bax in rheumatoid arthritis synovium.
OBJECTIVE
The aim of this study was to analyze the expression of apoptosis-related molecules in rheumatoid arthritis (RA) synovium, with special emphasis on the apoptosis accelerator Bax.


METHODS
Immunohistochemical analysis of Bax, Bcl-2, and Bcl-x(L) was performed in tissue specimens of patients with RA and compared to normal synovial tissue. Expression of Bax was additionally determined by double labeling with CD68, p53, and Ki-67 (clone MIB-1). Apoptotic cells were further identified by the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method.


RESULTS
In RA, expression of Bax was higher than in healthy controls and occurred in CD68-positive and -negative synoviocytes. Strong Bax staining was also found in chondrocytes at sites of cartilage degradation. Bax-positive synoviocytes could be detected with p53 and also with Ki-67. Bax and Bcl-x(L) were markedly colocalized in synovium. The TUNEL method revealed only few positive synoviocytes.


CONCLUSIONS
The marked colocalization of Bax and antiapoptotic Bcl-x(L) as well as the low frequency of TUNEL-positive cells in RA synovium suggest that Bax activity is not sufficient to decrease synovial hyperplasia in RA. Apoptotic mechanisms in RA chondrocytes might also be important for the pathogenesis of joint damage.
Hilbers
Insa
I
Institute of Pathology, University of Mainz, 55101 Mainz, Germany.
Hansen
Torsten
T
Petrow
Peter K
PK
Gaumann
Andreas
A
Bräuer
Rolf
R
Salzmann
Günther
G
Gay
Renate E
RE
Kosmehl
Hartwig
H
Kirkpatrick
C James
CJ
Gay
Steffen
S
Kriegsmann
Jörg
J
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D005260:Female; D019254:Genes, bcl-2 / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein