The expression and function of complement inhibitory protein CD55 in chronic rhinosinusitis with nasal polyp

Abstract

Abstract Background The factors that regulating classic complement activation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely unknown. CD55 functions as a complement regulatory protein by inhibiting the formation of C5 convertases. Objectives To investigate the expression, regulation, and function of CD55 in CRSwNP. Methods The expression of CD55 in sinonasal mucosal samples was investigated by quantitative RT-PCR, Western blotting, and immunofluorescence. The levels of C3d and C5b-9 in nasal tissue homogenates were analyzed by ELISA. Primary human nasal epithelial cells were cultured to investigate the regulation and function of CD55. Results The mRNA and protein levels of CD55 were reduced in eosinophilic nasal polyps compared with those in noneosinophilic nasal polyps and control tissues. CD55 was prominently expressed by nasal epithelial cells in sinonasal mucosa, which was downregulated by IL-4, IL-13, and Dermatophagoides pteronyssinus group 1. The levels of C3d and C5b-9 were upregulated in eosinophilic nasal polyps and were inversely correlated with CD55 expression levels. The conversion of C3 to C3d by primary human nasal epithelial cells was enhanced in those from eosinophilic nasal polyps in comparison to those from noneosinophilic polyps. The mRNA and protein expression of E-cadherin and ZO-1 were downregulated in eosinophilic nasal polyps and were positively correlated with CD55 expression levels. Conclusion The reduced expression of CD55 caused by local type 2 milieu lead to hyperactivation of complement and subsequent C5b-9 formation, which may further disrupt epithelial integrity in patients with eosinophilic CRSwNP.