Differential Expression of Adhesion Molecules by Sinonasal Fibroblasts among Control and Chronic Rhinosinusitis Patients

Abstract

Background Chronic rhinosinusitis (CRS) is characterized by inflammatory cell migration into sinus tissue with resultant inflammation fueled by a milieu of cytokines. Fibroblasts may contribute to inflammation through expression of leukocyte adhesion molecules such as vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM). VCAM attracts eosinophils and mast cells contributing to Th2 skewing, and ICAM attracts neutrophils and to a lesser degree, eosinophils, and contributes to mixed Th1/Th2 skewing. The purpose of this study was to compare sinus fibroblast adhesion molecule expression ex vivo among CRS subtypes and in vitro after cytokine stimulation. Methods Sinus biopsy specimens were taken from control patients (n = 13), CRS without nasal polyposis (CRSsNP, n = 6), and CRS with nasal polyposis (CRSwNP, n = 15). Ex vivo levels of VCAM and ICAM were measured by flow cytometry from single cell suspensions of tissue biopsy specimens. Changes in VCAM and ICAM expression to cytokine exposure were assessed using in vitro cultured sinonasal fibroblasts treated with tumor necrosis factor (TNF)-α, interleukin (IL)-4, or interferon (IFN)-γ. Results Ex vivo VCAM expression was lowest in controls, higher in CRSsNP, and highest in CRSwNP. In vitro stimulation with TNF-α and IL-4, but not IFN-γ, increased VCAM among CRSsNP, while expression in CRSwNP remained elevated with all treatments except IFN-γ. Ex vivo ICAM expression was elevated in both CRS subtypes. In vitro stimulation with TNF-α and IFN-γ, but not IL-4, increased ICAM expression in all patients with the largest effects among the CRSsNP subgroup. Conclusion Sinonasal fibroblast expression of adhesion molecules in sinusitis varies by disease state and is selectively influenced by exposure to inflammatory cytokines.