Abstract
BackgroundAlthough epidemiological studies reveal that cigarette smoke (CS) facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.MethodsWild type (WT) and CD44 knock-out (KO) mice were exposed simultaneously to house dust mite (HDM) extract and CS. Inflammatory cells, hyaluronic acid (HA) and osteopontin (OPN) levels were measured in bronchoalveolar lavage fluid (BALF). Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th) 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.ResultsIn WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS)/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.ConclusionWe demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.
Highlights
Asthma, a chronic inflammatory disease of the airways, is often linked to allergen exposure
In Wild type (WT) mice, combined house dust mite (HDM)/cigarette smoke (CS) exposure increased the number of inflammatory cells and the levels of hyaluronic acid (HA) and OPN in bronchoalveolar lavage fluid (BALF) and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS)/CS, HDM/Air or PBS/Air
CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice
Summary
A chronic inflammatory disease of the airways, is often linked to allergen exposure. It is well known that exposure to mainstream or secondhand cigarette smoke (CS) increases the risk of asthma development, and raises asthma-related morbidity and disease severity [2]. Animal models that combine allergen exposure with environmental pollutants such as CS better reflect the reality where (allergic) asthmatics are exposed to active and/or passive smoking in daily life. We described a murine model of CS-facilitated sensitization and aggravation of allergic airway inflammation to HDM [4] in which CS exposure increased many asthma features such as eosinophilia, Th2 cytokine production and goblet cell metaplasia. Epidemiological studies reveal that cigarette smoke (CS) facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation
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