Purpose Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly characterized by eosinophil- and T helper 2 cell (Th2)-biased inflammation. Integrins and intercellular adhesion molecules (ICAMs) are superfamilies of cell adhesion molecules (CAMs) that facilitate the recruitment and trafficking of immune cells and have been implicated in coordinating eosinophil and Th2 cell adhesion and signaling in asthma. The roles of CAMs in CRSwNP, however, remain poorly understood. The purpose of this study was to characterize the systemic and local expression of CAMs and identify which CAMs are potentially involved in CRSwNP pathology. Materials and Methods A prospective observational study was conducted using peripheral blood and anterior ethmoid tissues of patients with CRSwNP (n=32) and controls (n=15). Multiplex gene analysis and Pearson correlations were performed to identify associations between systemically and locally expressed CAMs. Based on the gene expression results, immunohistochemical evaluation and quantification of cells expressing integrins ITGAM, ITGAX, and ITGB2, as well as ICAM-3 in sinonasal tissues were conducted to compare local protein expression patterns. Results Integrin and ICAM genes were significantly elevated in the blood ( p <0.001 to p <0.05) and sinuses ( p <0.0003 to p <0.05) of patients with CRSwNP compared to controls. Strong positive correlations of genes expressed in the blood ( p <0.01 to p <0.05) and sinuses ( p <0.01) were observed between ITGAM, ITGAX, ITGB2 , and ICAM3 . ITGAM-, ITGB2-, ICAM-3-, and ICAM-3/ITGB2-positive cell counts were significantly increased in CRSwNP compared to controls ( p <0.0001 to p <0.04), and a positive correlation between ICAM-3/ITGB2- and ITGAM-positive cell counts was observed ( p <0.02). Conclusion The systemic and local expression of ITGAM, ITGB2, and ICAM-3 is significantly upregulated in CRSwNP, suggesting that integrin complex ITGAM/ITGB2 and ICAM-3 serve a potential role in inflammation-mediated signaling in CRSwNP.

Background Altered neovascularity is typically observed in chronic inflammatory diseases with overlapping pathophysiology to that observed in chronic rhinosinusitis (CRS). However, characterization of these inflammatory‐induced vascular‐mediated changes in CRS is limited. Understanding the underlying vascular changes in CRS will allow for strategic design and development of new drug‐delivery technologies that exploit vascular permeability for increased extravasation into the target sinonasal tissues. Methods Patients with CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and non‐CRS controls were enrolled in this prospective, observational study. The extent of angiogenesis in tissue was characterized using immunohistochemical and multiplex gene expression analyses. Vascular permeability, interendothelial junction structures, and endothelial barrier morphology were evaluated using transmission electron microscopy. Results Sinonasal vascularity was increased significantly in CRSsNP and CRSwNP (p < 0.05) when compared with controls, as assessed by enumerating the platelet endothelial cell adhesion molecule (PECAM‐1)‒positive blood vessels. Pro‐angiogenic gene expression, including PECAM1 and platelet‐activating factor receptor, was elevated significantly in patients with CRSwNP when compared with controls (p < 0.05). The fenestration sizes between endothelial cells (17‐280 nm) were larger in CRSwNP compared with CRSsNP (10‐33 nm) patients and controls (4‐12 nm). Global thinning of the endothelial cell lining was observed in CRS patients but not in controls. Conclusion Significant increases in vascularity, the pro‐angiogenic gene, and protein expression and blood vessel morphogenesis were observed in CRS patients compared with controls. In addition, fenestration sizes between interendothelial junction structures were larger in CRS patients than in controls, suggesting inflammation‐driven vascular dysregulation in CRS pathology.

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