Interactions via α2β1 Cell Integrin May Protect against the Progression of Airway Structural Changes in Asthma

Abstract

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.

Increased Oxidative Stress in Asthma—Relation to Inflammatory Blood and Lung Biomarkers and Airway Remodeling Indices

“…Unfortunately, in this study, we did not collect those data in the control group. However, compared to control datasets in our previous report [ 27 ], which was conducted by using a similar methodology, CT imaging parameters suggest mild-to-moderate changes in airway geometry (10% difference on average, p < 0.05), whereas RBM thickness is ~30% thicker in asthmatics compared to controls ( p < 0.001). In Figure 1 , we depict representative pictures of RBM measures in control and asthma individuals.…”

Co-Expression Analysis of Airway Epithelial Transcriptome in Asthma Patients with Eosinophilic vs. Non-Eosinophilic Airway Infiltration

“…Endobronchial biopsy tissue specimens were processed routinely, as described in our previous publications [ 69 ]. The 2 µm paraffin-embedded sections were cut and stained with hematoxylin and eosin.…”