Complement-eosinophil axis participates in fibrin deposition in eosinophilic chronic rhinosinusitis

Background: Eosinophilic chronic rhinosinusitis (ECRS) is characterized by intense eosinophil infiltration and excessive fibrin formation in the nasal polyps (NPs). The role of the complement system in the pathogenesis of ECRS is not well understood. Objective: This study aimed to evaluate the potential role of complement components in the pathogenesis of NPs. Methods: : We measured the levels of thrombin/anti-thrombin complex (TATc), C3a, C5a, galectin-10, and IL-5 proteins in the sinonasal tissue using enzyme-linked immunosorbent assay (ELISA). The effects of the complement components on human eosinophils were evaluated in terms of cell death and regulation of the coagulation system in vitro. Results: : TATc, C3a, C5a, galectin-10, and IL-5 levels in NPs were significantly higher in ECRS-NPs than in uncinate process tissue (UT) samples. The levels of C5a, galectin-10, and IL-5 were also significantly higher in ECRS-NPs than in non-ECRS-NPs. A significant correlation was observed between the levels of both C3a and C5a and those of TATc, galectin-10, or IL-5. Eosinophil extracellular trap-forming cell death (EETosis) was spatially co-localized with fibrin deposition in NP tissue. In vitro, co-stimulation with C5a and IL-5 induced EETosis, leading to the exposure of phosphatidylserine due to plasma membrane disruption. C5a and IL-5 also amplified tissue factor gene expression in eosinophils. Conclusions: : Elevated levels of complement components in the nasal tissues of patients with ECRS may participate in eosinophil activation, which facilitates fibrin deposition in NPs.