Abstract
Enhanced contractility and migration of airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF) are part of airway remodeling in asthma. Eosinophils are the central inflammatory cells that participate in airway inflammation. However, the role of asthmatic eosinophils in ASMC and PF contractility, migration, and differentiation to contractile phenotype has not yet been precisely described. A total of 38 individuals were included in this study: 13 steroid-free non-severe allergic asthma (AA) patients, 11 severe non-allergic eosinophilic asthma (SNEA) patients, and 14 healthy subjects (HS). For AA patients and HS groups, a bronchial allergen challenge with D. pteronyssinus was performed. Individual combined cell cultures were prepared from isolated peripheral blood eosinophils and immortalized ASMC or commercial PF cell lines separately. The migration of ASMC and PF was evaluated using wound healing assay and contractility using collagen gel assay. Gene expression of contractile apparatus proteins, COL1A1, COL5A1, and FN, in ASMC and PF was evaluated using qRT-PCR. We found that contractility and migration of ASMC and PF significantly increased after incubation with asthmatic eosinophils compared to HS eosinophils, p < 0.05, and SNEA eosinophils demonstrated the highest effect on contractility of ASMC and migration of both cell lines, p < 0.05. AA and SNEA eosinophils significantly increased gene expression of contractile apparatus proteins, COL1A1 and FN, in both cell lines, p < 0.05. Furthermore, the allergen-activated AA eosinophils significantly increased the contractility of ASMC, and migration and gene expression in ASMC and PF, p < 0.05. Thus, asthmatic eosinophils change ASMC and PF behavior by increasing their contractility and migration, contributing to airway remodeling.
Highlights
In recent years, growing numbers of asthma patients and uncontrolled episodes indicate the need for fundamental asthma pathogenesis studies [1]
The study results showed that asthmatic eosinophils promoted airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF)-induced collagen gel shrinkage, increased migration of ASMC and PF cells, and promoted their differentiation into a more contractile phenotype
The gene expression of main extracellular matrix (ECM) proteins such as COL1A1, FN, and contractile phenotype markers such as α-sm-actin, sm-myosin light chain (MHC), SM22, and sm-myosin light chain kinase (MLCK) for ASMC, and α-sm-actin for PF cells, increased in both cell lines after co-culture with asthmatic eosinophils; the highest effect was produced with severe non-allergic eosinophilic asthma (SNEA) eosinophils
Summary
In recent years, growing numbers of asthma patients and uncontrolled episodes indicate the need for fundamental asthma pathogenesis studies [1]. The thickened airway wall is composed of structural cells, deposited extracellular matrix (ECM) proteins, and migrated inflammatory cells. Structural lung cells, such as airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF), are the synthetically and mechanically active cells that quickly respond to airway inflammation by changing their behavior via the release of various biologically active mediators, production of ECM proteins, and increased contraction and migration. Altered contractility and migration of ASMC and PF are part of airway inflammatory processes that contribute to airway remodeling in asthma. Allergic sensitization of human airways results in increased levels of myosin light chain kinase (MLCK), which phosphorylates the myosin light chain (MHC) and leads to ASMC contraction [7].
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