Changes in Mouse Lung Morphology following Exposure to Brevetoxin-3

 

Kelli L. Margot1, James C. Ryan2, Frances M. Van Dolah1,2, John E. Baatz1, and Eric R. Lacy1

 

1 Marine Biomedicine and Environmental Sciences Center, Medical University of South Carolina, Charleston, SC.

2 Marine Biotoxins Program, NOAA Center for Coastal Environmental Health and Biomolecular Research, Charleston, SC

 

 

Marine algal toxins are produced worldwide and include some of the world’s most lethal biotoxins.  Brevetoxins, produced by the red tide causing organism Karenia brevis, elicit a variety of health threats including neurotoxic shellfish poisoning and lung irritation.  Brevetoxins are released into the water and aerosolized by wave action, allowing inhalation of these toxins.  Aerosolized brevetoxins are particularly harmful to lungs due to their lipophilic nature, which allows them to be distributed throughout the lung via surfactant.  Although detrimental effects such as airway constriction and suppression of lung immune responses have been attributed to aerosolized brevetoxins, the mechanism of brevetoxin effects on the lung has not been thoroughly described.  The hypothesis tested here was that systemic exposure to brevetoxin could lead to inflammation of the lung tissue.  Female ICR mice were given 180μg/kg brevetoxin-3 by intraperitioneal injection.  Four hours after injection, mice were sacrificed and lungs were removed for analysis.  Paraffin embedded lungs were sectioned and stained.  Here, I show that intraperitioneal brevetoxin exposure may contribute to lung inflammation.  Hematoxylin and eosin staining showed inflammation in the treated lungs compared to control lungs.  Additional peroxidase stains indicate an increase in the number of alveolar macrophages upon brevetoxin-3 exposure, as well as changes in the expression of proSP-C, which is used as a marker for alveolar epithelial type II (AEII) cells.  From this initial trial we conclude that systemic brevetoxin exposure leads to lung inflammation, and the effects of brevetoxins on lung cells warrants further investigation.