Abstract
Background: Understanding the pathophysiology of severe asthma is essential for the development of novel therapies. Carcinoembryonic antigen cell adhesion molecule (CEACAM) family members are expressed in healthy lung tissue, and have properties that suggest they may play a role in asthma pathophysiology. Objective: To explore the gene expression, tissue distribution and cellular provenance of CEACAM6 in asthma. Methods: CEACAM6 gene and protein expression were investigated using RNA microarrays and immunohistochemistry respectively on bronchial biopsy tissue obtained from healthy control subjects, and patients with asthma. Soluble CEACAM6 was measured in sputum and blood by ELISA. Results: CEACAM6 gene expression in bronchial biopsies was increased in severe asthma and was not related to expression of a Th2 gene signature. CEACAM6 protein expression was increased in airway epithelial cells and lamina propria inflammatory cells in severe asthma. CEACAM6 in the lamina propria was localised to neutrophils predominantly, but also eosinophils and macrophages. Neutrophil density in the bronchial mucosa was similar across health and the spectrum of asthma severity, but the percentage of neutrophils expressing CEACAM6 was significantly increased in severe asthma. CEACAM6 gene and epithelial protein expression correlated with epithelial MUC5AC protein expression. Conclusion: CEACAM6 expression is increased in severe asthma and primarily associated with airway epithelial cells and tissue neutrophils. CEACAM6 may contribute to the pathology of treatment-resistant asthma via neutrophil and airway epithelial cell-dependent pathways.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have