Gradual increase in priming of human eosinophils during extravasation from peripheral blood to the airways in response to allergen challenge

Background: Eosinophils isolated from the blood of patients with allergic asthma exhibit enhanced responsiveness to multiple stimuli compared with cells from normal controls, a phenomenon generally referred to as priming. This priming response is essential for optimal activation with augmented responses including chemotaxis, cytotoxicity, respiratory burst, and the release of proinflammatory lipid mediators. Objective: To monitor the kinetics of priming of eosinophils in the peripheral blood and in the bronchoalveolar lavage fluid of patients with allergic asthma before and after allergen challenge. Methods: Priming of blood eosinophils obtained from patients with allergy and donors without allergy was measured by labeling with monoclonal phage antibodies A17 and A27 recognizing priming-associated epitopes on phagocytes. In addition, blood and bronchoalveolar lavage fluid eosinophils from subjects with allergy after segmental and whole lung allergen challenge were similarly analyzed. Results: A dose-dependent cytokine-induced upregulation of priming-associated epitopes on blood eosinophils was found. Patients with allergic asthma exhibited an in vivo partially primed eosinophil phenotype, which is further primed in vitro after cytokine or chemokine incubation. Priming was increased in peripheral blood 6 hours after whole lung challenge as well as after segmental allergen challenge. Interestingly, eosinophils obtained from the bronchoalveolar lavage fluid 48 hours after segmental allergen challenge exhibited a higher primed phenotype. Conclusion: These data are consistent with a model in which local allergic inflammatory reactions induce partial systemic eosinophil priming in the peripheral blood. Eosinophils found in the airway are highly primed, consistent with the markedly upregulated inflammatory capacity observed in these cells.