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Increased alveolar macrophage chemiluminescence and airspace cell superoxide production in active pulmonary
W J Calhoun1, S M Salisbury, L W Chosy
1Department of Medicine, University of Wisconsin, Madison 53792.
Abstract:
Alveolar macrophages (AMs) and lymphocytes are activated in pulmonary sarcoidosis. Mediators from these cells are potentially important in the pathophysiology and pathogenesis of this disease. To determine whether the enhanced release of reactive oxygen species (ROS) participates in inflammatory events in sarcoidosis, and to explore the relationship between ROS release and clinical parameters, we studied ROS metabolism of AMs and other airspace cells by luminol-enhanced chemiluminescence and by direct biochemical measurement of superoxide anion production. Ten of 17 patients with sarcoidosis were prospectively found to have active disease by objective radiographic, functional, and laboratory criteria. In these subjects, ROS metabolism by AMs was significantly enhanced compared either with healthy control subjects or with patients with inactive sarcoidosis. Abnormalities in ROS metabolism were not seen in peripheral blood monocytes, suggesting that this increased metabolic activity is compartmentalized to the lung. Enhanced ROS metabolism by AMs was associated with recent adverse chest radiographic changes, recent decline in forced vital capacity, and more advanced radiographic type. These data support the hypothesis that ROS generated by airspace cells can promote parenchymal inflammation in sarcoidosis, are associated with physiologic and radiologic changes, and may thereby contribute to the pathogenesis of sarcoidosis.
Insights
Reactive oxygen species (ROS) release from alveolar macrophages is elevated in active pulmonary sarcoidosis. This enhanced ROS metabolism correlates with lung inflammation and disease severity.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Pulmonary sarcoidosis involves activated alveolar macrophages and lymphocytes.
- Mediators released by these cells may drive disease pathophysiology.
- The role of reactive oxygen species (ROS) in sarcoidosis pathogenesis is unclear.
Purpose of the Study:
- To investigate if enhanced ROS release contributes to inflammation in sarcoidosis.
- To explore the link between ROS release and clinical parameters in sarcoidosis patients.
Main Methods:
- Studied ROS metabolism in alveolar macrophages (AMs) and other airspace cells.
- Utilized luminol-enhanced chemiluminescence and direct superoxide anion production assays.
- Compared ROS metabolism in patients with active sarcoidosis, inactive sarcoidosis, and healthy controls.
Main Results:
- Significantly enhanced ROS metabolism was observed in AMs of patients with active sarcoidosis compared to controls and inactive disease.
- Abnormal ROS metabolism was compartmentalized to the lungs, not seen in peripheral blood monocytes.
- Elevated ROS metabolism in AMs correlated with adverse radiographic changes, decreased forced vital capacity, and advanced radiographic type.
Conclusions:
- Enhanced ROS generation by airspace cells supports the hypothesis of promoting parenchymal inflammation in sarcoidosis.
- ROS metabolism abnormalities are linked to physiological and radiological changes in sarcoidosis.
- ROS may play a significant role in the pathogenesis of pulmonary sarcoidosis.