Abstract
Eosinophilic inflammation is one of the main pathophysiological features in asthma. Two subtypes of eosinophils exist in the lung and systemic circulation: lung-resident eosinophils (rEOS) and inflammatory eosinophils (iEOS). We evaluated the expression of α4β1 and αMβ2 integrins of eosinophil subtypes and their influence on airway smooth muscle (ASM) cell proliferation and viability in asthma. We included 16 severe non-allergic eosinophilic asthma (SNEA) patients, 13 steroid-free, non-severe allergic asthma (AA) patients, and 12 healthy control subjects (HS). For AA patients, a bronchial allergen challenge with Dermatophagoides pteronyssinus was performed. The eosinophil subtypes were distinguished using magnetic bead-labeled antibodies against surface CD62L, and individual combined cell cultures were prepared with ASM cells. The integrins gene expression was analyzed by a quantitative real-time polymerase chain reaction. Proliferation was assessed by the Alamar blue assay, and viability by annexin V and propidium iodide staining. rEOS-like cells were characterized by the relatively higher gene expression of the β1 integrin subunit, whereas iEOS-like cells were characterized by the αM and β2 integrin subunits. The inclusion of either eosinophil subtypes in co-culture significantly increased the proliferation of ASM cells, and the effect of rEOS-like cells was stronger than iEOS-like cells (p < 0.05). Furthermore, rEOS-like cells had a more pronounced effect on reducing ASM cell apoptosis compared to that of iEOS-like cells (p < 0.05). Lastly, the bronchial allergen challenge significantly enhanced only the iEOS-like cells’ effect on ASM cell proliferation and viability in AA patients (p < 0.05). These findings highlight the different expression of α4β1 and αMβ2 integrins on distinct eosinophil subtypes in asthma. Therefore, rEOS-like cells have a stronger effect in stimulating ASM cell proliferation and viability; however, contact with specific allergens mainly enhances pro-proliferative iEOS-like cell properties.
Highlights
In the severe non-allergic eosinophilic asthma (SNEA) group, the airway smooth muscle (ASM) cell number in the co-culture with resident eosinophils (rEOS)-like cells was increased by 33.2% ± 9.4%, and by 18.7% ± 5.6% with inflammatory eosinophils (iEOS), compared to ASM cells that increased by 33.2% ± 9.4%, and by 18.7% ± 5.6% with iEOS, compared to ASM cells that had not been co-incubated with eosinophils (p < 0.05)
24 h of co-culture and presented the results in comparison with those of control ASM cells without incubation with eosinophils; rEOS-like cells isolated from SNEA patients had without incubation with eosinophils; rEOS-like cells isolated from SNEA patients had a a more pronounced effect in reducing ASM cell apoptosis compared to the AA and healthy control subjects (HS)
Cells through co-culture, and this effect of asthmatic cells exceeded that of healthy ones; rEOS-like cells had stronger pro-proliferative properties compared with that of iEOS-like cells, the bronchial challenge with the D. pteronyssinus allergen significantly enhanced the pro-proliferative properties of iEOS-like cells without affecting rEOS-like cells in AA patients
Summary
Asthma is a chronic inflammatory lung disease that globally affects more than 300 million people It is characterized by activated inflammatory cells, increased inflammatory mediators, airway hyperresponsiveness, intermittent or fixed airway obstruction, and airway remodeling [1]. A crucial part of the pro-proliferative effect of eosinophil subtypes could be their direct adhesion through integrins on ASM cells or released extracellular matrix proteins. We speculated that rEOS-like and iEOS-like cells could differ in their effects on the proliferation and apoptosis of ASM cells in asthma. As we know that allergen-provoked acute asthma episodes could not affect the pro-proliferative properties of eosinophil subtypes [4], we hypothesized that a bronchial allergen challenge with D. pteronyssinus might result in accelerated eosinophil subtype-related development of airway remodeling during acute asthma. We sought to determine if the distinct eosinophil subtypes, rEOS-like and iEOS-like cells, could possess different integrin expression patterns
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