Abstract
Harmful algal blooms (HABs) are focal, dense aggregations of large numbers of planktonic organisms ("blooms") that often are associated with production of biotoxins and cause harm to marine organisms and ecosystems. Florida red tide (causative dinoflagellate Karenia brevis) is one of the most notorious of all HABs, occurring on a virtually annual basis along Florida's Gulf coast. Brevetoxins (biotoxins produced by K. brevis) are potent neurotoxins. Florida red tide causes major epizootics, produces toxic shellfish when the dinoflagellate is filter-accumulated in clams and oysters, and releases an irritating toxicant into the air when surf conditions are turbulent.The aim of this thesis is two-fold: first, to characterize an animal model of human brevetoxin aerosol exposure using a sheep model of compromised airways; and second, to begin addressing and identifying the cellular and immunologic consequences of brevetoxicosis using an in-vitro system. Sub-acute, 4-day exposure to pure brevetoxin-3 results in a marked, neutrophilic pulmonary inflammatory response and airway hyper-responsiveness in both allergic and non-allergic sheep. In addition, in-vivo and in-vitro experiments suggest that there are variable, but demonstrable, immunomodulatory effects of brevetoxin exposure on peripheral neutrophil and alveolar macrophage viability, function, and mediator activity. These data were novel in that this is the first animal model to show pulmonary physiologic, inflammatory, and cellular effects of exposure to environmentally relevant concentrations of aerosolized PbTx-3. The in-vitro studies provide basic and preliminary information on brevetoxicosis on the cellular level from which investigations of potential mechanisms of action may be pursued.