Antimicrobial and Defense Proteins in Chronic Rhinosinusitis with Nasal Polyps

Abstract

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) presently remains a difficult disease to manage. Antimicrobial and defense proteins are important factors that could help characterize the role of microorganisms in CRSwNP pathogenesis, as the concept of microbial dysbiosis in CRS is still being considered. Our aim is to investigate the complex appearance, relative distribution and interlinks of human β defensin 2 (HBD-2), human β defensin 3 (HBD-3), human β defensin 4 (HBD-4), and cathelicidin LL 37 (LL 37) in chronic rhinosinusitis with nasal polyps (CRSwNP)-affected human nasal mucosa. Materials and Methods: The study group consisted of 48 samples from patients with CRSwNP. Samples were collected during functional endoscopic sinus surgery. The control group consisted of 17 normal healthy nasal mucosa samples gathered during routine septoplasty. β-defensin-2, β-defensin-3, β-defensin-4 and cathelicidin LL 37 in tissue were detected via immunohistochemical analysis. Results: HBD-2, HBD-3 and LL 37 were significantly decreased in epithelial cells in both primary and recurrent nasal polyp samples (p < 0.001) in comparison to control samples. HBD-2 was decreased in the subepithelial connective tissue of primary nasal polyp samples when compared to both recurrent polyp (p = 0.050) and control (p = 0.033) samples. In subepithelial connective tissue, significantly more HBD-3-positive structures were observed in primary nasal polyp samples (p = 0.049) than in control samples. In primary polyp samples, moderate correlations between connective tissue HBD-3 and connective (R = 0.584, p = 0.001) and epithelial tissue LL 37 (R = 0.556, p = 0.002) were observed. Conclusions: Decreased HBD-2, HBD-3 and LL 37 concentrations in the epithelium suggest a dysfunction of the epithelial barrier in patients with nasal polyps. Decreased subepithelial connective tissue HBD-2 suggests different responses to nasal microbiota in patients with primary nasal polyps compared to recurrent nasal polyps. Increased HBD-3 in subepithelial connective tissue suggests a possible role of this antimicrobial peptide in the pathogenesis of primary nasal polyps.

Local Defense Factors in Cleft-Affected Palate in Children before and during Milk Dentition Age: A Pilot Study

“…It is also noted that both HBD-2 and HBD-3 share similar anti-inflammatory functions by increasing chemokine and cytokine secretion, proliferation of epithelial and connective tissue cells, like fibroblasts and keratinocytes, as well as promoting wound and damaged tissue healing [32,50]. Similar to a study by Viksne et al, the positive correlation of HBD-2 and HBD-3 in our study could be connected to changed functions of the epithelial barrier in the cleft-affected tissue for patients before or during milk dentition [49]. Moreover, a statistically significant moderate positive correlation was also identified between the quantity of HBD-3 positive structures in the epithelium and HBD-2 positive structures in the connective tissue.…”

“…A statistically notable strong positive correlation was established between the quantity of HBD-2 and HBD-3 positive structures in the epithelium. The synergy of both peptides has been previously observed in other cases of chronic inflammation, like periodontitis, chronic rhinosinusitis, and COPD [33,48,49]. It is also noted that both HBD-2 and HBD-3 share similar anti-inflammatory functions by increasing chemokine and cytokine secretion, proliferation of epithelial and connective tissue cells, like fibroblasts and keratinocytes, as well as promoting wound and damaged tissue healing [32,50].…”

Endotypes of Chronic Rhinosinusitis with Primary and Recurring Nasal Polyps in the Latvian Population

“…We discussed the distribution of these very biomarkers in our previous publications, where we analyzed the distributions of cytokines, proliferation marker Ki 67, and antimicrobial and defense proteins in the tissues of recurrent and primary nasal polyps and compared them to the control samples of healthy nasal mucosa. Significant differences were found, showing decreased biomarker presence in epithelial cells and increased presence in the subepithelial connective tissue of nasal polyps compared to the control samples [14][15][16]. With the addition of clinical parameters, we were able to characterize five different clusters of patients with similar individual distributions of biomarkers.…”

“…Samples of nasal polyps were taken during planned functional endoscopic sinus surgery (FESS). As for the control samples, we previously published and characterized control group samples taken from the healthy nasal mucosa of patients undergoing septoplasty in our previous studies [14][15][16]. The research proposal was reviewed and approved by the ethics committee of Riga Stradins University (6-1/10/59.…”

Remodeling of Paranasal Sinuses Mucosa Functions in Response to Biofilm-Induced Inflammation

“…Journal of Inflammation Research 2024:17 1310 in subepithelial connective tissue, suggesting its role in the pathogenesis of primary nasal polyps. 188 Conversely, elevated calprotectin levels in nasal polyp tissues may reflect neutrophil recruitment as a compensatory mechanism. 189 Calprotectin (CP) exerts proinflammatory responses via TLR4, IL-8, and TNF-α, as well as anti-inflammatory and tissueprotective functions, such as inhibition of MMPs by sequestration of zinc and PAR-2-mediated antioxidative effects.…”