Cathelicidin LL-37 in bronchoalveolar lavage and epithelial lining fluids from healthy individuals and sarcoidosis patients

Abstract

Sarcoidosis is a granulomatous disease of unknown etiology most often characterized by pulmonary manifestations. Changes in an innate immune system, involving antimicrobial peptides, have been noted during the course of pulmonary sarcoidosis. This study focuses on the level of LL-37 peptide, the only human cathelicidin, additionally characterized by a wide range of pleiotropic activities, in pulmonary sarcoidosis. A cross-sectional study was conducted in groups of 32 patients with sarcoidosis and 12 healthy individuals. Bronchoalveolar lavage fluid (BALF) sampling, followed by LL-37 measurements by mass spectrometry combined with previous immunoaffinity purification, was performed. Based on urea levels, concentrations of LL-37 in epithelial lining fluid (ELF) were calculated. The levels of LL-37 peptide in BALF samples derived from patients with pulmonary sarcoidosis (median: 17.45 pg/ml, 25th–75th percentile: 8.05-28.33 pg/ml) were significantly higher compared to the healthy group (median: 6.38 pg/ml, 25th–75th percentile: 4.90-11.55 pg/ml) (U Mann-Whitney test, p=0.04). Assessment of LL-37 in ELF confirmed the differences across the groups that were observed in BALF. The level of LL-37 in patients with sarcoidosis (median: 2.25 ng/ml, 25th–75th percentile: 1.03-5.06 ng/ml) was again higher compared to healthy individuals (median: 0.62 ng/ml, 25th-75th percentile: 0.43-2.17 ng/ml) (p=0.06, Mann-Whitney U test). The results of this study demonstrate that the level of LL-37 peptide is elevated in pulmonary compartment affected by sarcoidosis. This might have a meaning in the pathomechanism of the disease, especially taking into consideration versatile activity of human cathelicidin revealed in numerous experimental studies during the last years.