Expression of activated FcγRll discriminates between multiple granulocyte-priming phenotypes in peripheral blood of allergic asthmatic subjects

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:120

Article

Kanters, Deon ; ten Hove, Willem ; Luijk, Bart ; van Aalst, Corneli ; Schweizer, Rene C. ; Lammers, Jan-Willem J. ; Leufkens, Hubert G. M. ; Raaijmakers, Jan A. M. ; Bracke, Madelon ; Koenderman, Leo

关键词: priming;    allergen challenge;    neutrophils;    eosinophils;    allergic asthma;    gene expression;    peripheral blood;   

DOI  :  10.1016/j.jaci.2007.06.021

来源: Elsevier

【 摘 要 】

Background: Allergic asthma is associated with chronic airway and systemic immune responses. Systemic responses include priming of peripheral blood eosinophils, which is enhanced after allergen challenge. In a subpopulation of asthmatic subjects, neutrophils are associated with bronchial inflammation. Objective: We sought to monitor systemic granulocyte priming in allergic asthmatic subjects as a consequence of chronic and acute inflammatory signals initiated by allergen challenge. Methods: Blood was taken at baseline and 6 to 24 hours after allergen challenge in asthmatic subjects with and without late asthmatic responses. Systemic granulocyte priming was studied by using expression of cellular markers, such as alpha-chain of Mac-1 (alpha m)/CD11b, L-selectin/CD62L, and an activation epitope present on Fc gamma RII/CD32 recognized by monoclonal phage antibody A17. Results: Eosinophils of asthmatic subjects have a primed phenotype identified by cell-surface markers. Neutrophils of these patients were subtly primed, which was only identified after activation with N-formyl-methionyl-leucyl-phenylaianine. After allergen challenge, an acute increase in eosinophil priming characterized by enhanced expression of activated Fc gamma RII was found in patients experiencing a late asthmatic response and not in patients with a single early asthmatic response. In contrast, expression of alpha m/CD11b and L-selectin on granulocytes was not different between control and asthmatic subjects and was not affected by allergen challenge. Interestingly, expression of both adhesion molecules was positively correlated, and alpha m expression on eosinophils and neutrophils correlated positively with bronchial hyperresponsiveness. Conclusion: Different phases, phenotypes, or both of allergic asthma are associated with distinct priming profiles of inflammatory cells in peripheral blood. Clinical implications: Insight in differences of systemic innate responses will lead to better definition of asthma subtypes and to better designs of new therapeutic options.

【 授权许可】

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