Elevated alpha-defensin levels in plasma of patients with pulmonary sarcoidosis
Jun-Ichi Ashitani1, Nobuhiro Matsumoto, Masamitsu Nakazato
1Third Department of Internal Medicine, Miyazaki University School of Medicine, Miyazaki, Japan. jashi2@fc.miyazaki-u.ac.jp
Background And Objectives:
Pathogens such as mycobacteria and proprionibacterium have been implicated in the pathogenesis of sarcoidosis. alpha-Defensins (DF) are naturally occurring antimicrobial peptides. The aim of the present study was to assess whether DF are increased in the airway and/or systemic circulation in patients with pulmonary sarcoidosis and whether DF levels are related to sarcoidosis disease activity.
Methods:
DF levels in plasma and BAL fluid (BALF) were measured in 30 patients with pulmonary sarcoidosis and in 10 controls. Plasma and BALF DF levels were compared according to disease activity. Molecular forms were analysed using reverse-phase (RP) HPLC to confirm plasma and BALF DF kinetics in pulmonary sarcoidosis.
Results:
DF concentrations in plasma and BALF were higher in patients with pulmonary sarcoidosis than in the controls. Plasma DF levels correlated with lysozyme but not with angiotensin-converting enzyme. These levels were high in patients in whom more organs were involved, whereas BALF DF levels were higher in patients at stage II or III than with those at sarcoidosis I. RP-HPLC showed high plasma levels of pro-defensins, DF precursors from the bone marrow, in sarcoidosis, although DF in peripheral neutrophils and BALF were the mature type.
Conclusions:
High plasma DF concentrations resulted from bone marrow stimulation and seemed to be associated with disease activity, whereas BALF DF were released from accumulated neutrophils in the lungs and may contribute to parenchymal involvement in sarcoidosis.
Insights
Alpha-defensins (DF) are elevated in pulmonary sarcoidosis patients
Area of Science:
- Immunology
- Pulmonary Medicine
- Microbiology
Background:
- Sarcoidosis pathogenesis involves pathogens like mycobacteria.
- Alpha-defensins (DF) are antimicrobial peptides.
- DF's role in sarcoidosis requires further investigation.
Purpose of the Study:
- To determine if alpha-defensins (DF) are elevated in airway and systemic circulation of sarcoidosis patients.
- To investigate the relationship between DF levels and sarcoidosis disease activity.
Main Methods:
- Measured plasma and bronchoalveolar lavage fluid (BALF) DF levels in 30 sarcoidosis patients and 10 controls.
- Compared DF levels based on disease activity.
- Utilized reverse-phase HPLC to analyze DF molecular forms and kinetics.
Main Results:
- Plasma and BALF DF concentrations were significantly higher in sarcoidosis patients compared to controls.
- Elevated plasma DF levels correlated with multi-organ involvement and lysozyme, but not ACE.
- BALF DF levels were higher in stages II/III sarcoidosis compared to stage I.
Conclusions:
- Increased plasma DF likely originates from bone marrow stimulation and correlates with sarcoidosis activity.
- BALF DF, released from neutrophils, may contribute to lung tissue involvement in sarcoidosis.
