Journal of Asthma and Allergy (May 2021)

Cell Adhesion Molecules are Upregulated and May Drive Inflammation in Chronic Rhinosinusitis with Nasal Polyposis

  • Blight BJ,
  • Gill AS,
  • Sumsion JS,
  • Pollard CE,
  • Ashby S,
  • Oakley GM,
  • Alt JA,
  • Pulsipher A

Journal volume & issue
Vol. Volume 14
pp. 585 – 593

Abstract

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Brennan J Blight, Amarbir S Gill, Jorgen S Sumsion, Chelsea E Pollard, Shaelene Ashby, Gretchen M Oakley, Jeremiah A Alt, Abigail Pulsipher Division of Otolaryngology-Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USACorrespondence: Abigail PulsipherDivision of Otolaryngology-Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery, University of Utah School of Medicine, 50 North Medical Drive, Room 3C120, Salt Lake City, UT, 84132, USAEmail [email protected]: 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.Keywords: integrins, intercellular adhesion molecule 3, macrophage-1 antigen, Th2 pathophysiology, transcriptional analysis, allergy, asthma

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