Re. Santing et al., THE IMPORTANCE OF EOSINOPHIL ACTIVATION FOR THE DEVELOPMENT OF ALLERGEN-INDUCED BRONCHIAL HYPERREACTIVITY IN CONSCIOUS, UNRESTRAINED GUINEA-PIGS, Clinical and experimental allergy, 24(12), 1994, pp. 1157-1163
Using a newly developed guinea-pig model of asthma, characterized by a
llergen-induced early and late phase asthmatic reactions, bronchial hy
perreactivity (BHR) and airway inflammation, the importance of eosinop
hil activation for the development of BHR to inhaled histamine was inv
estigated at 6 h (after the early reaction) and 24 h (after the late r
eaction) after allergen provocation. Eosinophil activation was assesse
d by a sensitive kinetic assay for eosinophil peroxidase (EPO) activit
y, suitable for bronchoalveolar lavage (BAL) analysis. A significant 2
.9-fold (P < 0.01) increase in bronchial reactivity to histamine was o
bserved at 6 h after allergen exposure, which was associated with a 2.
9-fold increase in the number of eosinophils (P < 0.05) and a 6.7-fold
increase in EPO activity (P < 0.01) in the BAL fluid. At 24 h after a
llergen exposure the bronchial reactivity to histamine was lower (1.7-
fold), but still significantly enhanced (P < 0.01). By contrast, the n
umber of eosinophils was further increased compared with 6h after prov
ocation (3.8-fold, P < 0.05), while the EPO activity remained stable a
t 6h levels. The number of eosinophils was significantly correlated wi
th EPO activity at 6 h (r = 0.62; P < 0.05), but not at 24 h after pro
vocation. No significant correlation was observed between the number o
f eosinophils in the BAL fluid and BHR to histamine at either time poi
nt. Remarkably, EPO activity was significantly correlated to BHR at 24
h (r = 0.66; P < 0.004), but not at 6h after provocation. These result
s indicate that: newly infiltrated eosinophils have the highest activa
tion state during the early asthmatic reaction; EPO may play a role in
the development of BHR to inhaled histamine after the late reaction a
nd that besides EPO, additional mechanisms may contribute to BHR to hi
stamine after the early asthmatic reaction.