Esnault Stephane, Kelly Elizabeth A, Sorkness Ronald L, Evans Michael D, Busse William W, Jarjour Nizar N
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
School of Pharmacy, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
J Allergy Clin Immunol. 2016 Mar;137(3):767-73.e6. doi: 10.1016/j.jaci.2015.05.053. Epub 2015 Oct 30.
Coagulation Factor XIII (FXIII) plays an important role in wound healing by stabilizing fibrin clots and cross-linking extracellular matrix proteins. FXIII is expressed in cells of the monocyte/macrophage and dendritic cell lineages in response to type 2 cytokines.
We sought to determine the association between FXIII and asthma pathobiology.
We analyzed the expression of FXIII mRNA and protein levels in bronchoalveolar lavage samples obtained before and after segmental allergen challenge from patients with mild asthma and in induced sputum samples collected from patients with mild-to-moderate and severe asthma.
FXIII mRNA and protein levels were highly upregulated in bronchoalveolar cells and fluid after allergen challenge and mRNA levels correlated with protein levels. In sputum of asthmatic patients, FXIII expression was positively correlated with type 2 immune response and dendritic cell markers (CD209 and CD207). FXIII expression was also associated with increased airflow limitation (FEV1/forced vital capacity and residual volume/total lung capacity ratios) and greater reversibility to β-agonists.
FXIII expression was upregulated in the airways of asthmatic patients after allergen exposure. Expression in the sputum of asthmatic patients correlated with the type 2 immune response and airflow limitation. Excessive activity of FXIII could contribute to the pathophysiology of airway obstruction in asthmatic patients.
凝血因子 XIII（FXIII）通过稳定纤维蛋白凝块和交联细胞外基质蛋白在伤口愈合中发挥重要作用。FXIII 在单核细胞/巨噬细胞和树突状细胞谱系的细胞中响应 2 型细胞因子而表达。
我们试图确定 FXIII 与哮喘病理生物学之间的关联。
我们分析了轻度哮喘患者在节段性过敏原激发前后获得的支气管肺泡灌洗样本以及轻度至中度和重度哮喘患者收集的诱导痰样本中 FXIII mRNA 和蛋白水平的表达。
过敏原激发后，支气管肺泡细胞和液体中 FXIII mRNA 和蛋白水平高度上调，且 mRNA 水平与蛋白水平相关。在哮喘患者的痰液中，FXIII 表达与 2 型免疫反应和树突状细胞标志物（CD209 和 CD207）呈正相关。FXIII 表达还与气流受限增加（第一秒用力呼气容积/用力肺活量和残气量/肺总量比值）以及对β激动剂的更大可逆性相关。
哮喘患者气道中过敏原暴露后 FXIII 表达上调。哮喘患者痰液中的表达与 2 型免疫反应和气流受限相关。FXIII 的过度活性可能导致哮喘患者气道阻塞的病理生理学。
