Cathelicidin related antimicrobial peptide, laminin, Toll-like receptors and chemokines levels in experimental hypersensitivity pneumonitis in mice.

INTRODUCTION: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by unresolved inflammation and tissue repair pathologies triggered by repeated organic dust exposure. The aim of the study was to investigate changes in levels of the cathelicidin related antimicrobial peptide (CRAMP), laminin (LAM-A1), selected Toll-like receptors (TLR) and chemokines in experimental HP in mice. MATERIALS AND METHODS: Three and 18-month-old female C57BL/6J mice underwent inhalations of the saline extract of Pantoea agglomerans cells, Gram-negative bacterium common in organic dust and known for its pathogenic impact. The inhalations were repeated daily (28 days). ELISA was used for measuring in lung tissue homogenates concentration of CRAMP, LAM-A1, TLR2, TLR4, TLR8, CXCL9 (chemokine [C-X-C motif] ligand) and CXCL10. RESULTS: Levels of TLR2, TLR4 and CXCL9 were significantly higher in both young and old mice lungs already after 7 days of inhalations, while significant increase of LAM-A1 and CXCL10 was noted after 28 days, compared to untreated samples. TLR8 level was significantly augmented only in young mice. Only CRAMP level significantly declined. Significantly higher TLR8 and CXCL9 concentration in untreated samples were noted in old animals compared to young ones. CONCLUSION: Significant alterations of the examined factors levels indicate their role in HP pathogenesis.

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

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.

Relationship between COPD and lower socioeconomic status in farmers from South-Eastern Poland (Lublin region).

INTRODUCTION: Lower socioeconomic status is considered to be an independent risk factor of chronic conditions, such as chronic obstructive pulmonary disease (COPD). COPD, one of the major public health problems worldwide, is a chronic inflammatory lung disease of a multifactorial background. COPD morbidity in rural areas has been higher than in urban settings, as apart from the major causative factor, tobacco smoking, the burden of this disease in rural environments is also connected to additional occupational factors (organic dusts). The management of chronic diseases seems to be particularly difficult in rural areas. The aim of the study was to analyze the socioeconomic status of farmers suffering from COPD in comparison to healthy farmers. METHODS: Thirty farmers with COPD and 34 healthy farmers from the Lublin region (Poland) were investigated based on the area of land they possessed (an indicator used in the health insurance system in Poland to classify farmers). The farmers from five rural communes were selected by general practitioners. Statistical analysis was performed by non-parametric Mann-Whitney U-test for the differences between area of farms. The p < 0.05 level was considered as significant. RESULTS: Area of land (median: 1.5 ha, 25th-75th percentile: 1.0-4.0) owned by farmers with COPD was significantly lower than area of farms belonging to healthy farmers (median: 7.0 ha, 25th-75th percentile: 3.0-10.0) (p < 0001, Mann-Whitney U-test). CONCLUSIONS: In rural areas individuals with COPD are characterized by significantly lower socioeconomic status than healthy persons. COPD is a major health problem, especially in rural areas, which may indicate that policy-makers should consider addressing equity in COPD management in rural areas.

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

Innate immunity is currently under scope of interest concerning its role in the development of chronic obstructive pulmonary disease (COPD). Antimicrobial peptides constitute a potent part of this fast response system. Here, we focus on the role of a specific antimicrobial peptide, the only human cathelicidin, the pleiotropic LL-37 peptide, in the development of COPD under clinical conditions. A cross-sectional study was conducted in groups of 43 patients with COPD (previously classified according to GOLD) 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. Additionally, an antimicrobial assay of growth inhibition of two bacterial species, often involved in COPD development mechanisms, by purchased LL-37 was conducted. Altogether, 55 BALF samples were analyzed. LL-37 levels were significantly higher in BALF from patients in early stages of COPD (GOLD I-II) compared to BALFs from healthy individuals. The same was true for ELF. Cathelicidin’s concentration was significantly lower in both BALF and ELF from patients in advanced COPD (GOLD III-IV). The significantly elevated LL-37 levels both in BALF and ELF in patients with COPD at stage GOLD I-II together with reduced levels in advanced (COPD stage III-IV) further supports the innate immunity involvement in COPD pathology and suggests a profound change in non-specific immunity during the disease progression.