Octavio M. Oliva; Veena B. Antony, M.D.; Rajesh Jagirdar, M.S.; and Douglas Watson, Ph.D. University of Alabama at Birmingham, Birmingham, AL
Bronchial epithelial cells are the primary barrier to inhaled environmental pollutants. Corexit 9500A, in an aerosolized form, was employed as a dispersant in the recent Gulf Oil Spill (2010). There is evidence suggesting that personnel involved in the cleanup effort may have been exposed to airborne Corexit. We hypothesize that Corexit increases epithelial monolayer permeability, alters cell morphology and induces anoikis. This hypothesis was corroborated in-vitro via inoculation of a transform bronchial epithelial cell line (BEAS-2B) with Corexit 9500A. In particular, alterations in epithelial marker E-cadherin, EphA2 - EFNA1 (receptor ligand complex) and Caspase-3 as a marker of apoptosis were explored. For phenotypic studies, we used cell counting with an emphasis on changes in cell shape (cell diameter) using a cell counter. Finally, we employed electric cell-substrate impedance signaling (ECIS) as a model to evaluate permeability of the epithelial monolayer by obtaining capacitance and resistance measurements. The results obtained demonstrate that Corexit 9500A instigates gross morphological changes of cell shape and dimensions. Corexit induces an increase in the expression of E-Cadherin, EphA2, EFNA1 and Caspase-3. These changes are associated with an inflammatory response, increase in bronchial permeability and the secretion of vascular endothelial growth factor (VEGF). Furthermore, ECIS results showed a decrease in monolayer attachment and overall resistance with increasing doses of Corexit. Thus, we concluded that the injury sustained by the bronchial epithelial monolayer is one that involves its localized separation from the basal membrane via focal adhesion kinase (FAK) ligation. In response to this process, the epithelial cells strengthened the horizontal cell-to-cell junctions by up-regulating E-cadherin as well as undergoing a reduction in overall cell volume. Eventually, this cellular detachment led to the onset of anoikis and a concomitant increase in bronchial epithelial monolayer permeability.