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Acute inflammatory responses to Stachybotrys chartarum in the lungs of infant rats: time course and possible
Iwona Yike1, Thomas G Rand, Dorr G Dearborn
1Mary Ann Swetland Center for Environmental Health, Case Western Reserve University, Cleveland, Ohio 44106-3029, USA. ixy@po.cwru.edu
Abstract:
Stachybotrys chartarum has been linked to building-related respiratory problems including pulmonary hemorrhage in infants. The macrocyclic trichothecenes produced by S. chartarum have been the primary focus of many investigations. However, in addition to trichothecenes this fungus is capable of producing other secondary metabolites and a number of protein factors. This study examines the effects of intact, autoclaved, and ethanol-extracted spores on the lungs of infant rats as an approach to differentiate between secondary metabolites and protein factors. Seven-day-old infant rats were exposed intratracheally to 1 x 10(5) spores/g body weight (toxic strain JS58-17) and sacrificed at various times up to 72 h. The inflammatory response was measured by morphometric analysis of the lungs and determination of inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid. Alveolar space was greatly reduced in animals exposed to fungal spores compared to phosphate buffered saline (PBS)-treated controls. The largest effects were observed in pups treated with intact spores where alveolar space 24 h after treatment was 42.1% compared to 56.8% for autoclaved spores, 51.1% for ethanol-extracted spores, and 60.6% for PBS-treated controls. The effects of different spore preparations on inflammatory cells, cytokine, and protein concentrations in the BAL fluid can be ranked as intact > autoclaved > extracted. Tumor necrosis factor alfa (TNF-alpha), interleukin 1-beta (IL-1beta), and neutrophils were the most sensitive indicators of inflammation. The difference between autoclaved (100% trichothecene toxicity, denatured/enzymatically inactive proteins) and intact (100% trichothecene activity, unaltered/released proteins) spores indicates the involvement of fungal proteins in the inflammatory response to S. chartarum and sheds new light on the clinical importance of "nontoxic" strains.
Insights
Stachybotrys chartarum spores cause lung inflammation in infant rats. Both fungal proteins and toxins contribute to this response, impacting respiratory health.
Area of Science:
- Environmental microbiology
- Toxicology
- Pulmonary medicine
Background:
- Stachybotrys chartarum is associated with building-related respiratory issues.
- Macrocyclic trichothecenes are primary toxins studied, but other factors exist.
- Differentiating toxin vs. protein effects is crucial for understanding health impacts.
Purpose of the Study:
- To investigate the role of Stachybotrys chartarum secondary metabolites and protein factors in lung inflammation.
- To differentiate the inflammatory effects of intact, autoclaved, and ethanol-extracted spores in infant rats.
Main Methods:
- Infant rats were intratracheally exposed to S. chartarum spores (intact, autoclaved, extracted) or PBS.
- Lung morphometric analysis and bronchoalveolar lavage (BAL) fluid analysis were performed.
- Inflammatory cells, cytokine concentrations (TNF-alpha, IL-1beta), and protein levels were measured.
Main Results:
- Fungal spores significantly reduced alveolar space compared to controls.
- Inflammatory effects ranked: intact spores > autoclaved spores > extracted spores.
- TNF-alpha, IL-1beta, and neutrophils were sensitive indicators of inflammation.
Conclusions:
- Both trichothecenes and fungal proteins contribute to S. chartarum-induced lung inflammation.
- Autoclaved spores (trichothecenes active, proteins inactive) showed significant inflammation, indicating protein involvement.
- Findings highlight the clinical importance of fungal proteins, even in "nontoxic" strains.
