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- Title
LL‐37 promotes neutrophil extracellular trap formation in chronic rhinosinusitis with nasal polyps.
- Authors
Cao, Yujie; Chen, Fenghong; Sun, Yueqi; Hong, Haiyu; Wen, Yihui; Lai, Yinyan; Xu, Zhaofeng; Luo, Xin; Chen, Yang; Shi, Jianbo; Li, Huabin
- Abstract
Background: Neutrophil accumulation has been observed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the functions of neutrophils are poorly understood. Neutrophils produce neutrophil extracellular traps (NETs), which are involved in a variety of chronic inflammatory pathologies. LL‐37 is the only member of the cathelicidin family in human. Objective: Our aims were to examine the presence of NETs in CRSwNP and to investigate the regulatory effect of LL‐37 on NET formation. Methods: Nasal polyp tissues were investigated for the presence of NETs by using immunofluorescent (IF) staining. The expression and distribution of LL‐37 were examined by using quantitative RT‐PCR, ELISA, IF, and immunohistochemistry. Purified peripheral neutrophils were stimulated with LL‐37 and stained with IF to identify NETs. NETs% was defined as percentage of NET‐generating neutrophils to the total number of neutrophils. Results: Neutrophil extracellular traps were located in the subepithelial layer of nasal polyps and control tissues. Nasal polyps had higher NETs% compared with that of controls (23.01% ± 3.43% vs 4.52% ± 1.33%, P < 0.0001). NET count was also increased in nasal polyps. NET count correlated with neutrophil count (r = 0.908, P < 0.001). LL‐37 protein and mRNA levels were upregulated in nasal polyps. LL‐37 was distributed in the epithelial and subepithelial layer and mainly expressed by neutrophils. Moreover, LL‐37 promoted peripheral neutrophils to form NETs in a dose‐dependent manner ex vivo. Interestingly, dexamethasone did not inhibit the effect of LL‐37 on inducing NET formation. Furthermore, peripheral neutrophils from CRSwNP patients were more susceptible to LL‐37‐mediated NET formation, compared with neutrophils derived from control subjects. In addition, NETs released LL‐37 in vivo and ex vivo. Conclusion: Neutrophil extracellular traps are significantly increased in nasal polyps and LL‐37 induces NET formation in CRSwNP patients. These findings indicate that NETs may contribute to the pathogenesis of neutrophilic inflammation in CRSwNP.
- Subjects
NASAL polyps; SINUSITIS; NEUTROPHILS; TRAPPING
- Publication
Clinical & Experimental Allergy, 2019, Vol 49, Issue 7, p990
- ISSN
0954-7894
- Publication type
Article
- DOI
10.1111/cea.13408