Translocation of Ricin Across Polarized Human Bronchial Epithelial Cells

摘要

Due to widespread availability, toxicity, and potential for use as a bioterrorism agent, ricin is classified as a category B select agent. While ricin can be internalized by a number of routes, inhaled ricin is particularly problematic. The resulting damage leads to irreversible pulmonary edema and death. Our study describes a model system developed to investigate the effects of ricin on repiratory epithelium. Human bronchial (HBE) cells were cultured on collagen IV inserts until polarized epithelial cell monlayers developed. Ricin was added to the apical or basal medium and then damage to the cell monlayer was assessed. Within a few hours after exposure, ricin damaged HBE cells, rendering the cell monolayer permeable to the paracellular passage of ricin. A mouse anti-ricin antibody neutralized ricin and prevented cellular damage if the antibody was present before ricin bound to the epithelial cells. These studies suggested that, to be effective, therapeutic agents or antibodies neutralizing ricin biological activity must be present at the apical surface of epithelial cells. The in vitro system developed here provides a method by which to screen potential therapeutics for their ability to protect lung epithelial cells from ricin intoxication.