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Toxicological Sciences 65, 239-245 (2002)
Copyright © 2002 by the Society of Toxicology


RESPIRATORY TOXICOLOGY

Microanatomical Changes in Alveolar Type II Cells in Juvenile Mice Intratracheally Exposed to Stachybotrys chartarum Spores and Toxin

T. G. Rand*,1, M. Mahoney*, K. White* and M. Oulton{dagger}

* Department of Biology, Saint Mary's University, 923 Robie Street, Halifax, Nova Scotia, Canada B3H 3C3; and {dagger} Department of Physiology and Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada B3J 3G9

Stachybotrys chartarum is an important environmental fungus. We have shown recently that alveolar type II cells are sensitive to exposure to Stachybotrys chartarum spores and to the trichothecene, isosatratoxin-F, both in vitro and in vivo, in a juvenile mouse model. This sensitivity is manifest as significant changes in the composition and normal metabolic processing of pulmonary surfactant. This study evaluated the effects of a single intratracheal exposure of S. chartarum spores and toxin on ultrastructure and dimensions of alveolar type II cells from juvenile mice. This was to determine whether there are concurrent morphological and dimensional changes in the alveolar type II cell that reflect the metabolic alterations in pulmonary surfactant that we observed in the treated mice. Marked ultrastructural changes were associated with alveolar type II cells in both S. chartarum and isosatratoxin-F treated animals compared to untreated, saline, and Cladosporium cladosporioides spore treated animals. These ultrastructural changes included condensed mitochondria with separated cristae, scattered chromatin and poorly defined nucleolus, cytoplasmic rarefaction, and distended lamellar bodies with irregularly arranged lamellae. Point count stereological analysis revealed a significant increase (p < 0.05) in lamellar body volume density in S. chartarum and isosatratoxin-treated animals after 48 h exposure. Mitochondria volume density was significantly lower in the isosatratoxin-F (48 h exposure) and S. chartarum treated (24 and 48 h exposure) animals compared to those in the other treatment groups. These results reveal that exposure to S. chartarum spores and toxin elicit cellular responses in vivo differently from those associated with exposure to spores of a nontoxigenic mold species. They also indicate that accumulation of newly secreted pulmonary surfactant in the alveolar space of S. chartarum and isosatratoxin-F treated animals might be a consequence of cellular trauma resulting in lamellar body volume density changes leading to increased release of pulmonary surfactant into the alveolar space.

Key Words: ultrastructure; alveolar type II cells; Stachybotrys chartarum; trichothecenes; intratracheal instillation; fungal conidia; morphometrics.


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