The Inflammatory Process in Nasal Polyposis: Genetics, Molecular Biology, and Electrophysiology

Abstract

Nasal polyposis is the ultimate manifestation of chronic inflammation in the lateral wall of the nose. At least two factors that may lead to the development of inflammation in the lateral wall of the nose are (1) genetic polymorphism of inflammatory genes, particular the A allele at position −308 in the promotor region of the TNF-α gene and (2) the production of exotoxins by Staphylococcus aureus and their ability to upregulate the variable β (V_β) region of the TCR of lymphocytes. Cytokines in nasal polyps drive the inflammatory response. TNF-α can upregulate VCAM-1 (vascular cell adhesion molecule-1), which is a major counterreceptor for the integrins on the surface of both lymphocytes and eosinophils. TNF-α can also be released by eosinophils, resulting in an autocrine upregulation of eosinophils into the nasal polyp. Eosinophils release major basic protein, a granular protein that is capable of increasing net sodium flux across the apical surface of the nasal polyp epithelium, resulting in increased water absorption and the ultimate development of edema, a major histopathological feature of polyposis. The increased number of open sodium channels, known to exist in both CF epithelium and non-CF polyp epithelium, can be abrogated by the use of topical diuretics such as amiloride and furosemide.