Multiple Granulocyte Priming Phenotypes In Peripheral Blood Of Allergic Asthmatics
The Journal of Allergy and Clinical Immunology(2007)
摘要
RATIONALE: 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 asthmatics neutrophils are associated with bronchial inflammation. The objective of this study was to monitor granulocyte priming in allergic asthmatics as consequence of chronic and acute inflammatory signals initiated by allergen challenge.METHODS: Blood was taken at baseline and 6-72h after allergen challenges in asthmatics with and without late asthmatic responses (LAR). Systemic granulocyte priming was studied using 1) expression of cellular markers such as αm (CD11b), L-selectin and a priming epitope recognized by monoclonal phage antibody A17 and 2) gene expression profiles in neutrophils.RESULTS: Eosinophils of asthmatics have a primed phenotype identified using cellular surface markers. Neutrophils of asthmatics were subtle primed, which was only identified using gene expression profiling. After allergen challenge, an acute increase in eosinophil and neutrophil priming was found only in patients experiencing a LAR using priming markers and gene expression analysis, respectively. In contrast, granulocyte αm (CD11b) and L-selectin levels were not different between controls and asthmatics and not affected by allergen challenge. Interestingly, expression of both adhesion molecules was positively correlated and αm expression on eosinophils and neutrophils correlated positively with bronchial hyperresponsiveness.CONCLUSION: Different phases and/or phenotypes of allergic asthma are associated with distinct priming profiles of inflammatory cells in peripheral blood. Insight in differences of systemic innate responses will lead to better definition of asthma-subtypes and to better designs of new therapeutic options. RATIONALE: 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 asthmatics neutrophils are associated with bronchial inflammation. The objective of this study was to monitor granulocyte priming in allergic asthmatics as consequence of chronic and acute inflammatory signals initiated by allergen challenge. METHODS: Blood was taken at baseline and 6-72h after allergen challenges in asthmatics with and without late asthmatic responses (LAR). Systemic granulocyte priming was studied using 1) expression of cellular markers such as αm (CD11b), L-selectin and a priming epitope recognized by monoclonal phage antibody A17 and 2) gene expression profiles in neutrophils. RESULTS: Eosinophils of asthmatics have a primed phenotype identified using cellular surface markers. Neutrophils of asthmatics were subtle primed, which was only identified using gene expression profiling. After allergen challenge, an acute increase in eosinophil and neutrophil priming was found only in patients experiencing a LAR using priming markers and gene expression analysis, respectively. In contrast, granulocyte αm (CD11b) and L-selectin levels were not different between controls and asthmatics and not affected by allergen challenge. Interestingly, expression of both adhesion molecules was positively correlated and αm expression on eosinophils and neutrophils correlated positively with bronchial hyperresponsiveness. CONCLUSION: Different phases and/or phenotypes of allergic asthma are associated with distinct priming profiles of inflammatory cells in peripheral blood. Insight in differences of systemic innate responses will lead to better definition of asthma-subtypes and to better designs of new therapeutic options.
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关键词
peripheral blood,phenotypes
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