Airway factor XIII associates with type 2 inflammation and airway obstruction in asthmatic patients

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• 作者：Stephane Esnault ; PhD^a ; Elizabeth A. Kelly ; PhD^a ; Ronald L. Sorkness ; PhD^b ; Michael D. Evans ; MS^c ; William W. Busse ; MD^a ; Nizar N. Jarjour ; MD^a ; ^{nnj@medicine.wisc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Factor XIII ; asthma ; severe asthma ; allergy ; pulmonary function ; airway obstruction ; air trapping ; inflammation ; eosinophils ; IL-13
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：137
• 期：3
• 页码：767-773.e6
• 全文大小：737 K

文摘

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.

Objective

We sought to determine the association between FXIII and asthma pathobiology.

Methods

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.

Results

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.

Conclusions

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.