J. Zhu et al., Exacerbations of bronchitis - Bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants, AM J R CRIT, 164(1), 2001, pp. 109-116
Eosinophilia has been reported during exacerbations of bronchitis, but the
mechanisms of tissue recruitment of eosinophils are unclear. We quantified
eosinophils and the concurrent expression of cytokines and chemokines proba
bly responsible for the tissue eosinophilia in bronchial biopsies obtained
from three groups of non-atopic subjects: (1) healthy nonsmokers (n = 7; FE
V1 % predicted 108 +/- 4 [mean +/- SEM]); (2) nonasthmatic smokers with chr
onic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % pre
dicted: 75 +/- 5); and (3) nonasthmatic subjects with CB who sought medical
advice for an exacerbation of their condition (n = 9; FEV1 % predicted: 61
+/- 8). We applied anti-EG2 antibody and immunostaining to detect and coun
t eosinophils. We performed in situ hybridization to visualize and enumerat
e cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosino
phil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regul
ated on activation, normal T-cell expressed and secreted (RANTES). We confi
rmed an increase in EG2-positive eosinophils in patients with CB in exacerb
ation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, bu
t the between-group differences were not statistically significant. However
, the numbers of lymphomononuclear cells expressing eotaxin mRNA were signi
ficantly greater in the smokers with CB than in the healthy nonsmokers with
out CB (p < 0.01). Following an exacerbation, RANTES expression was upregul
ated and this chemokine was strongly expressed in both the surface epitheli
um and in subepithelial lymphomononuclear cells: only RANTES showed a signi
ficant positive correlation with the increasing number of EG2-positive cell
s (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation
can also occur in CB: the marked upregulation of RANTES in the epithelium a
nd subepithelium most likely accounts for the increased eosinophilia associ
ated with an exacerbation of bronchitis.