Inflammatory Endotypes And Tissue Remodeling Features In Antrochoanal Polyps

Purpose:The pathogenic mechanisms of antrochoanal polyps(ACPs)remain largely unknown.This study aimed to characterize the inflammatory pattern and tissue remodeling feature in ACPs.Methods:Inflammatory cell infiltration,tissue edema severity,and fibrin deposition in ACPs and bilateral eosinophilic and noneosinophilic nasal polyps(NPs)were studied with immunohistochemical and immunofluorescence staining.Cytokine levels in sinonasal tissues were detected with the Bio-Plex assay.The expression of coagulation and fibrinolytic markers was measured using reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assays.Human nasal epithelial cells were cultured with submerged method to explore the regulation of tissue plasminogen activator(t PA).Results:Compared with control tissues and bilateral eosinophilic and noneosinophilic NPs,ACPs had higher levels of neutrophil infiltration and expression of myeloperoxidase(MPO),interleukin(IL)-8 and interferon(IFN)-γ.In total,94.4%of ACPs demonstrated an eosinophil cationic protein/MPO ratio<1,compared to 79.0%of noneosinophilic and26%of eosinophilic NPs.Principle component and multiple correspondence analysis revealed a neutrophilic and type 1 inflammation pattern in ACPs.Compared to control tissues,edema scores and fibrin deposition were increased,whereas d-dimer and tissue plasminogen activator(t PA)levels were decreased in ACPs and bilateral NPs,with more prominent changes in ACPs even than in eosinophilic NPs.The t PA levels were negatively correlated with IFN-γ,IL-6,IL-8,and MPO levels in ACPs.IFN-γbut not IL-6significantly downregulated t PA expression in epithelial cells in vitro.Neutrophils were the major cellular source of IFN-γin ACPs,and the numbers of IFN-γ~+neutrophils were elevated in ACPs than those in control tissues and bilateral eosinophilic and noneosinophilic NPs.Conclusions:ACPs are characterized by neutrophilic and type 1 inflammation endotype.Neutrophil-derived IFN-γmay contribute to edema formation by suppressing t PA production in ACPs.