Quantitative analysis of apoptosis and bcl-2 in Sjögren's syndrome.
OBJECTIVE
To determine whether apoptosis plays a significant role in tissue damage of Sjögren's syndrome (SS).


METHODS
We performed a quantitative analysis of programmed cell death on salivary glands of 11 patients. Ten age matched women with sicca syndrome served as controls. Morphometric measurement of the fractional volume of acini and ducts showing DNA strand breaks was performed in sections stained by deoxynucleotidyl transferase assay. The extent of bcl-2 expression was determined in sections labeled with monoclonal antibody. The different cell populations infiltrating the glands were examined in tissues stained with anti-leukocyte common antigen and OPD4 monoclonal antibodies.


RESULTS
In patients with SS, 68% of the ductal epithelium was occupied by apoptotic structures, whereas only 12% of acini showed DNA strand breaks. Corresponding values in control salivary glands were 3 and 0.13%. bcl-2 labeling was higher in ducts than in acini of both control and pathologic glands. However, in SS a 43% (p < 0.001) and 75% (p < 0.001) reduction in bcl-2 expression was observed in ductal and acinar epithelium, respectively. In comparison with controls, the numerical density of CD4+ cells and plasma cells scattered throughout the interstitium was 323% and 203% higher (p < 0.001) in SS. Moreover, T helper/inducer lymphocytes represented 52% of the inflammatory foci.


CONCLUSIONS
Apoptosis occurs in minor salivary glands of patients with SS with a prevailing localization on the ductal epithelium in association with downregulation of bcl-2 and a large number of infiltrating CD4+ lymphocytes. Thus, the destruction of glandular tissue and the loss of secretory function in SS is dependent on the activation of the suicide program of epithelial cells.
Manganelli
P
P
Rheumatic Disease Unit, Hospital of Parma, Italy.
Quaini
F
F
Andreoli
A M
AM
Lagrasta
C
C
Pilato
F P
FP
Zuccarelli
A
A
Monteverdi
R
R
D'Aversa
C
C
Olivetti
G
G
D000368:Aged; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D004249:DNA Damage; D015536:Down-Regulation; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000378:metabolism / Q000473:pathology*
D019253:Proto-Oncogene Proteins c-bcl-2