Abstract
Background Allergic rhinitis (AR) is characterized by tissue and blood eosinophilia. Previous studies showed enhanced eosinophilia in allergic rhinitis patients with obesity, suggesting an association between obesity and eosinophilia. However, the interaction and mechanism between obesity and eosinophilia is still unclear. Methods We recruited thirty AR children and 30 controls in this study. Expression of leptin and osteopontin (OPN) proteins in serum was detected, and correlation analysis with eosinophilia was performed. The effect of leptin or OPN on eosinophil apoptosis, adhesion, migration, and activation of eosinophil was examined. Ovalbumin-sensitized mice were established to prove the role of obesity on eosinophil regulation by leptin and OPN. Results We found that upregulated serum and nasal leptin and OPN expression in AR were positively correlated with eosinophilia and eosinophil cationic protein levels. Leptin or OPN inhibited eosinophil apoptosis, demonstrated as inhibited DNA fragmentation and phosphatidylserine (PS) redistribution (P < 0.05). Leptin and OPN promote expression of cluster of differentiation 18 (CD-18) and intercellular adhesion molecule 1 (ICAM-1) and inhibit expression of ICAM-1 and L-selectin by eosinophils, which contribute to the adhesion of eosinophils. Leptin and OPN mediated migration and activation of eosinophil through phosphatidylinositol-3-OH kinase (PI3K) pathway. Obese AR mice presented with more severe eosinophilia and symptoms compared with nonobese AR mice or control mice. Immunochemistry staining of leptin and OPN of nasal turbinate in obese AR mice was also stronger than those in nonobese AR mice or control mice. Anti-OPN, anti-leptin, and anti-α4 treatments reduce nasal eosinophilia inflammation and clinical symptoms in model mice. Conclusion Our results suggested that in an obese state, upregulation of leptin and OPN regulates apoptosis, adhesion, migration, and activation of eosinophils, and this process may be mediated by the PI3K and anti-α4 pathways.
Highlights
Tissue and blood eosinophilia is a common feature in allergic airway diseases such as allergic rhinitis (AR), nasal polyposis, and bronchial asthma [1]
Our data indicated that serum leptin and OPN levels were significantly higher in Allergic rhinitis (AR) children compared with controls, especially in obese children (P < 0 05) (Figure 1)
The upregulated serum leptin and OPN levels were positively correlated with eosinophil counts (r = 0 66, P < 0 01; r = 0 59, P < 0 01) and Eosinophil Cationic Protein (ECP) concentration (r = 0 71, P < 0 01; r = 0 62, P < 0 01) in AR children, suggesting that leptin and OPN levels may be involved in eosinophil infiltration and activation (Figure 1)
Summary
Tissue and blood eosinophilia is a common feature in allergic airway diseases such as allergic rhinitis (AR), nasal polyposis, and bronchial asthma [1]. Delayed eosinophil apoptosis contributes to eosinophilia, and the infiltration and subsequent activation of eosinophils in the airways result in the secretion of specific granule proteins, synthesis, and release of lipid mediators, inflammatory cytokines, chemokines, and growth factors [2, 3]. Through these mediators, eosinophils contribute to the perpetuation and amplification of airway inflammation [4]. We found that upregulated serum and nasal leptin and OPN expression in AR were positively correlated with eosinophilia and eosinophil cationic protein levels. Our results suggested that in an obese state, upregulation of leptin and OPN regulates apoptosis, adhesion, migration, and activation of eosinophils, and this process may be mediated by the PI3K and anti-α4 pathways
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