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

Abstract

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.

Extracellular Vesicle ITGAM and ITGB2 Mediate Severe Acute Pancreatitis-Related Acute Lung Injury

“…SAP-EVs overexpress ITGAM and ITGB2 that heterodimerize to form integrin αmβ2 [also known as macrophage-1 antigen (Mac-1)], which is implicated in intercellular migration and adhesion processes, − but ITGA2B is related to coagulation response. , Thus, to individually evaluate the effect of ITGAM and ITGB2 on lung injury, we transfected human embryonic kidney 293T (HEK293T) cells with ITGAM or ITGB2 expression vectors or an empty expression cassette (negative control vector, NCV) (Figure A) to produce EVs that specifically overexpress one of these two integrins (EV ITGAM or EV ITGB2 ) or exhibit normal integrin expression (EV NCV ). Western blot analysis confirmed ITGAM or ITGB2 overexpression in the corresponding recombinant HEK293T cells and EV isolates versus cells transfected with negative control vector and their EVs (Figure B).…”

M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps

“…ITGB2 is a subunit of integrins extensively expressed in leukocytes which could conduct the extracellular signals and modulate cell responses such as cell adhesion, proliferation and differentiation ( 63 ). A recent study showed that ITGB2 was up-regulated in CRSwNP and might serve as an inflammatory mediator ( 64 ). TYROBP is a transmembrane polypeptide that regulate signal transduction in dendritic cells, macrophages and microglia.…”

Systematic analysis of prognostic significance, functional enrichment and immune implication of STK10 in acute myeloid leukemia

“…From a bioinformatics analysis, ITGAM and ITGB2 were also up-regulated in myeloma and involved in cytokine-cytokine receptor interaction, innate immune response and inflammatory response that were similar to our results [ 40 ]. Moreover, the integrin ITGAM/ITGB2, associated with immunity and inflammation [ 41 , 42 ], was gradually increased along with hematopoietic stem cells (HSC) differentiation in mice [ 41 ], suggesting the indirect role of STK10 in immune and defense. However, this view still needs to be verified by further studies.…”