Abstract
Previous studies have shown that quartz (crystalline silica) provides a useful tool to study experimental fibrosis in rodents. In the present study, we have investigated the involvement of phagocyte-derived reactive oxygen species (ROS) in quartz-induced inflammatory and fibrotic responses.
NADPH oxidase p47phox subunit deficient mice and their wild type counterparts were exposed to 100 mg/kg b.w. quartz via a single pharyngeal aspiration. After 24 hours markers of inflammation and oxidative stress were investigated in bronchoalveolar lavage fluid (BALF) and lung tissue. Quartz elicited a strong acute inflammatory response, characterised by a remarkably similar pulmonary influx of neutrophils in both strains. Interestingly, however, luminex multiplex analysis of BALF revealed stronger increases of interleukin (IL)-1β, IL-6, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein-1 (MCP-1) and granulocyte colony stimulating factor (G-CSF) in the knockout mice compared to wild type animals. Differences in IL-4, IL-10, IL-13 and tumour necrosis factor-alpha (TNF-α) were not detectable. In contrast, pulmonary mRNA levels of the oxidative stress markers γ-glutamyl cysteine synthetase (γ-GCS) and heme oxygenase-1 (HO-1) were significantly enhanced only in the wild type mice in response to quartz-treatment. Three months after quartz treatment, significantly less fibrosis occurred in the lungs of knockout mice, as indicated by hydroxyproline content and Masson's trichrome staining.
These data show that impairment of NADPH oxidase increases acute inflammatory responses, whereas it reduces oxidative stress and fibrosis in the lungs of quartz-exposed mice.
- © 2011 ERS