Kanters Deon, ten Hove Willem, Luijk Bart, van Aalst Corneli, Schweizer René C, Lammers Jan-Willem J, Leufkens Hubert G M, Raaijmakers Jan A M, Bracke Madelon, Koenderman Leo
Department of Pulmonary Diseases, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
J Allergy Clin Immunol. 2007 Nov;120(5):1073-81. doi: 10.1016/j.jaci.2007.06.021. Epub 2007 Aug 13.
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.
We sought to monitor systemic granulocyte priming in allergic asthmatic subjects as a consequence of chronic and acute inflammatory signals initiated by allergen challenge.
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.
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-phenylalanine. 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.
Different phases, phenotypes, or both 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.
过敏性哮喘与慢性气道和全身免疫反应相关。全身反应包括外周血嗜酸性粒细胞的致敏，在变应原激发后这种致敏会增强。在一部分哮喘患者中，中性粒细胞与支气管炎症有关。
我们试图监测过敏性哮喘患者因变应原激发引发的慢性和急性炎症信号而导致的全身粒细胞致敏情况。
在有或无迟发性哮喘反应的哮喘患者中，于基线时以及变应原激发后6至24小时采集血液。通过使用细胞标志物的表达来研究全身粒细胞致敏情况，这些标志物如Mac-1（αm）/CD11b的α链、L-选择素/CD62L，以及由单克隆噬菌体抗体A17识别的FcγRII/CD32上存在的活化表位。
哮喘患者的嗜酸性粒细胞具有通过细胞表面标志物确定的致敏表型。这些患者的中性粒细胞有轻微致敏，这仅在用N-甲酰甲硫氨酰亮氨酰苯丙氨酸激活后才能确定。变应原激发后，在经历迟发性哮喘反应的患者中发现以活化FcγRII表达增强为特征的嗜酸性粒细胞致敏急性增加，而在仅有早发性哮喘反应的患者中未发现。相比之下，对照患者和哮喘患者粒细胞上αm/CD11b和L-选择素的表达没有差异，且不受变应原激发的影响。有趣的是，两种黏附分子的表达呈正相关，嗜酸性粒细胞和中性粒细胞上的αm表达与支气管高反应性呈正相关。
过敏性哮喘的不同阶段、表型或两者与外周血中炎症细胞不同模式的致敏有关。
深入了解全身固有反应的差异将有助于更好地定义哮喘亚型，并有助于更好地设计新的治疗方案。
