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

ABSTRACT: 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 ?-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.

SUBMITTER: Esnault S

PROVIDER: S-EPMC5040212 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Esnault Stephane S Kelly Elizabeth A EA Sorkness Ronald L RL Evans Michael D MD Busse William W WW Jarjour Nizar N NN

The Journal of allergy and clinical immunology 20151030 3

<h4>Background</h4>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.<h4>Objective</h4>We sought to determine the association between FXIII and asthma pathobiology.<h4>Methods</h4>We analyzed the expression of FXIII mRNA and protein levels in bronchoalveolar lavage samples obtained be ...[more]

PMID: 26525229

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Project description:BACKGROUND:Differences in asthma severity may be related to inflammation in the airways. The lower airway microbiota has been associated with clinical features such as airway obstruction, symptom control, and response to corticosteroids. OBJECTIVE:To assess the relationship between local airway inflammation, severity of disease, and the lower airway microbiota in atopic asthmatics. METHODS:A cohort of young adult, atopic asthmatics with intermittent or mild/moderate persistent symptoms (n = 13) were assessed via bronchoscopy, lavage, and spirometry. These individuals were compared to age matched non-asthmatic controls (n = 6) and to themselves after six weeks of treatment with fluticasone propionate (FP). Inflammation of the airways was assessed via a cytokine and chemokine panel. Lower airway microbiota composition was determined by metagenomic shotgun sequencing. RESULTS:Unsupervised clustering of cytokines and chemokines prior to treatment with FP identified two asthmatic phenotypes (AP), termed AP1 and AP2, with distinct bronchoalveolar lavage inflammatory profiles. AP2 was associated with more obstruction, compared to AP1. After treatment with FP reduced MIP-1? and TNF-? and increased IL-2 was observed. A module of highly correlated cytokines that include MIP-1? and TNF-? was identified that negatively correlated with pulmonary function. Independently, IL-2 was positively correlated with pulmonary function. The airway microbiome composition correlated with asthmatic phenotypes. AP2, prior to FP treatment, was enriched with Streptococcus pneumoniae. Unique associations between IL-2 or the cytokine module and the microbiota composition of the airways were observed in asthmatics subjects prior to treatment but not after or in controls. CONCLUSION:The underlying inflammation in atopic asthma is related to the composition of microbiota and is associated with severity of airway obstruction. Treatment with inhaled corticosteroids was associated with changes in the airway inflammatory response to microbiota.

Dataset Information

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

Publications

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

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