Collections > Electronic Theses and Dissertations > Arsenic Compromises the Alveolocapillary Barrier, Facilitating Bacteremia in a Mouse Pneumonia Model

The greatest threat to public health regarding arsenic exposure is consumption of contaminated drinking water. Chronic oral consumption of inorganic arsenic has been linked with respiratory dysfunction as well as immunotoxicity. Here we examined the effects of consuming either of two concentrations of sodium arsenite (250 ppb, 25 ppm) via drinking water in a mouse model of bacterial pneumonia. Arsenic exposure did not alter recruitment of leukocytes to the airway upon bacterial infection, nor pulmonary clearance of bacteria, but was associated with increased dissemination to extrapulmonary tissues. Mice exposed to arsenic had intact bloodstream killing of bacteria, suggesting that the increased extrapulmonary bacterial burden in lung-infected mice derived from increased escape from the lung. Analysis of early events in lung-infected mice revealed that arsenic led to accelerated escape of bacteria from the alveoli, providing new evidence that chronic exposure to arsenic-contaminated drinking water disrupts the architecture of the alveoli, permitting pathogen escape into the bloodstream.