LL-37 promotes neutrophil extracellular trap formation in chronic rhinosinusitis with nasal polyps.
Cao. Yujie Y; Chen. Fenghong F; Sun. Yueqi Y; Hong. Haiyu H; Wen. Yihui Y; Lai. Yinyan Y; Xu. Zhaofeng Z; Luo. Xin X; Chen. Yang Y; Shi. Jianbo J; Li. Huabin H
Key Findings
- Nasal polyps contain more NETs and higher levels of LL-37 than healthy tissue.
- LL-37 directly triggers neutrophils to form NETs in a dose‑dependent way, and this is not blocked by dexamethasone.
- Neutrophils from patients with chronic rhinosinusitis with nasal polyps are more prone to LL-37‑induced NET formation.
Practical Outcomes
- For DIY health enthusiasts, the data suggest that boosting LL-37 (e.g., via supplements or topical agents) could increase inflammatory NETs in the sinuses, potentially worsening conditions like nasal polyps. It highlights a need for caution and monitoring of any interventions that raise LL-37 levels, especially for those prone to chronic sinus inflammation.
Summary
The study found that the natural peptide LL-37 is higher in nasal polyps and makes neutrophils release web‑like traps (NETs) that can worsen inflammation. This effect happens even when steroids are used, and people with the condition are more sensitive to LL-37.
Abstract
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. Our aims were to examine the presence of NETs in CRSwNP and to investigate the regulatory effect of LL-37 on NET formation. 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. 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. 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.
Study Information
pubmed
2019
2019-05-29T00:00:00.000Z
10.1111/cea.13408
36
38