Background-Eosinophils play a pivotal role in asthmatic airway inflammation
. Apoptosis is thought to be critically relevant in promoting the clearance
of inflammatory cells and the resolution of inflammation. Bcl-2 inhibits a
poptosis in cellular systems. A study was undertaken to determine whether b
cl-2 expression in sputum reflects the clinical severity of patients with a
sthma. The relationship between bcl-2 expression in sputum eosinophils and
eosinophil activation markers such as interleukin (IL)-5 and eosinophil cat
ionic protein (ECP) levels in sputum supernatant was evaluated.
Methods-Sputum was obtained from 18 patients with asthma. Fresh expectorate
d sputum separated from saliva was treated with an equal volume of dithioth
reitol 0.1%, cytospun for cell differentials and bcl-2 stain, and the super
natant was collected for biochemical assay. Bcl-2+ eosinophils were stained
using immunocytochemistry, ECP was measured by fluoroimmunoassay, and IL-5
was detected by sandwich enzyme linked immunosorbant assay.
Results-Twelve patients with severe or life threatening asthma had more bcl
-2+ eosinophils (mean difference 46.8% (95% CI 27.0 to 66.6), p<0.01) and a
higher ECP level (p<0.01) in the sputum than those with mild to moderate a
sthma (n = 6). IL-5 was frequently detected in patients with severe or life
threatening asthma (11/12 versus 1/6, p<0.01). There was a significant pos
itive correlation between bcl-2+ eosinophils and ECP levels (r = 0.61, p<0.
01) and between bcl-2+ eosinophils and IL-5 levels (r = 0.83, p<0.01). Ther
e was a significant negative correlation between bcl-2+ eosinophils and FEV
1/FVC (r = -0.54, p<0.05).
Conclusion-The increased expression of bcl-2 in eosinophils from sputum of
subjects with severe asthma suggests that bcl-2 may prolong survival and de
crease apoptosis of airway eosinophils in asthma.