Kinetics of eosinophilia and eosinophil activation in the development of non-allergic bronchial hyperresponsiveness in guinea pigs injected with Sephadex beads.
Eosinophils are believed to play a crucial role in the pathogenesis of airway hyperresponsiveness (AHR). In the present study, the involvement of blood and pulmonary eosinophilia as well as the eosinophil activation in the onset of non-allergic AHR caused by the injection of G-50 Sephadex beads in guinea pigs was investigated. Reactivity of the isolated lower bronchus to histamine was measured ex vivo in a bioassay system. The increase of reactivity of the isolated lower bronchus of Sephadex-injected animals to histamine was observed as early as 3 h after the Sephadex injection and was maximal between 6-24 h. Sephadex-induced blood eosinophilia was characterized by two successive increases of blood eosinophil counts peaking at 3 and 12 h respectively. The recruitment of inflammatory cells into the lungs as measured in bronchoalveolar lavage fluid (BALF) have shown that the neutrophils were initially increased at 3 h whereas the number of eosinophils increased only 6 h after the bead injection; both cell populations were maximal 24 h later. Eosinophil peroxidase (EPO) activity was used as a marker for the apparent number of eosinophils in airways and the degree of activation of eosinophils recovered in BALF. Results have shown that EPO activity in the lower bronchus of Sephadex-injected animals increased at 6 h, decreased at 12 h and was maximal 24 h later. The EPO activity recovered in BALF was maximal between 6 to 24 h after the bead injection in guinea pigs. Correlation between the number of eosinophils and the EPO activity in BALF suggests that BALF eosinophils have been activated and have degranulated in airways. Correlation studies also indicated that both Sephadex induced blood eosinophilia and eosinophil activation were associated to the development of AHR. In contrast, the increase of EPO activity in the lower bronchus and BALF eosinophilia were not correlated to the development of AHR in our model. In conclusion, our results suggest that Sephadex induced non-allergic AHR in guinea pigs could be related, at least in part, to blood eosinophilia and eosinophil activation. Whether blood, airway and BALF eosinophilia as well as eosinophil activation are relevant factors to determine the potential role of eosinophils in the pathogenesis of AHR is discussed.
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Canada.
K
K
Maghni
M J
MJ
Simard
D
D
Arseneault
P
P
Sirois
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003911:Dextrans; D004802:Eosinophilia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004804:Eosinophils / Q000473:pathology / Q000502:physiology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D010544:Peroxidases / Q000378:metabolism
D003911:Dextrans; D006632:Histamine; C025614:sephadex; D010544:Peroxidases