Toxicological Sciences 70, 98-109 (2002)
Copyright © 2002 by the Society of Toxicology
RESPIRATORY TOXICOLOGY |
An Extract of Stachybotrys chartarum Causes Allergic Asthma-like Responses in a BALB/c Mouse Model
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* Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606;
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 86 T. W. Alexander Drive, MD92, Research Triangle Park, North Carolina, 27711; and
National Exposure Research Laboratory, U.S. Environmental Protection Agency, Cincinnati, Ohio 45268
Environmental exposure to Stachybotrys chartarum has been associated with multiple adverse health effects in humans. The goal of this study was to assess soluble components of this fungus for their ability to cause an asthma-like response in a BALB/c mouse model. Five isolates of S. chartarum were combined and extracted to form a crude antigen preparation (S. chartarum extract 1 [SCE-1]). Female BALB/c mice were sensitized by involuntary aspiration of SCE-1 and subsequently reexposed at 2, 3, and 4 weeks. To distinguish immune from nonspecific inflammatory effects, mice were exposed to 3 doses of Hanks’ balanced salt solution (HBSS) and a final dose of SCE-1; or to 4 doses of bovine serum albumin (BSA) as a negative control protein. Serum and bronchoalveolar lavage fluid (BALF) were collected before the fourth aspiration (Day 0), and at Days 1, 3, and 7 following the final exposure, and lungs were fixed for histopathological examination. SCE-1-exposed mice displayed increased BALF total protein on Days 0, 1, and 3 and increased lactate dehydrogenase (LDH) at Days 1 and 3 only, compared to HBSS controls. BALF total cell numbers were elevated on each day, and differential counts of BALF cells showed neutrophilia on Day 1, marked eosinophilia on all days, and increased numbers of lymphocytes at Days 1, 3, and 7. Serum and BALF total IgE levels were elevated at all days, and BALF IL-5 levels were greatly increased (7-fold) on Day 1. Mice exposed to a single dose of SCE-1 exhibited inflammatory responses but not allergic responses, while BSA-treated mice showed neither inflammatory nor allergic responses. Histopathology confirmed the biochemical findings. Barometric whole-body plethysmography was performed 10 min prior to (baseline) and one h following each aspiration exposure in a second group of mice, to assess immediate respiratory responses. Airway hyperresponsiveness to increasing concentrations of nebulized methacholine (MCh) was assessed on Days 1 and 3 following the fourth aspiration exposure. Exposure to HBSS or BSA did not alter baseline enhanced pause (PenH) values or PenH following the aspiration exposures, nor did it cause an increase in airway responsiveness to MCh. Exposure to SCE-1 resulted in a 4.7-fold increase in PenH over baseline after the third exposure, increasing to 5.6-fold after the final exposure, and increased responsiveness to a 32 mg/ml MCh aerosol challenge. We conclude that multiple respiratory exposures to SCE-1 cause responses typical of allergic airway disease in this mouse model. However, BSA was nonallergenic and did not generate respiratory physiological responses when administered by aspiration.
Key Words: allergy; asthma; Stachybotrys chartarum; respiratory exposure.
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