Strain-related differences of nonspecific respiratory defense mechanisms in rats using a pulmonary infectivity model
J M Antonini1, J R Roberts, R W Clarke
1Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA. jga6@cdc.gov
Abstract:
A number of animal studies have assessed pulmonary host defense mechanisms by inoculating the lungs with the bacterial agent, Listeria monocytogenes. Most studies use only a single strain of the animal to be tested; however, strain-related differences in responsiveness to pulmonary toxicants have been well documented. It was the goal of this current investigation to measure the pulmonary defense responses of two different strains of rats in a lung infectivity model. Fischer 344 (F344) and Sprague-Dawley (SD) rats were instilled intratracheally with 5 x 10(3) or 5 x 10(5) L. monocytogenes, and the effect on mortality, lung injury and inflammation, pulmonary bacterial clearance, and alveolar macrophage (AM) function was determined at 3, 5, and 7 days after bacteria treatment. Pulmonary inoculation with the higher (5 x 10(5) L. monocytogenes) dose proved to be highly pneumotoxic to the F344 rats as evidenced by an increase in mortality and more severe lung injury and inflammation when compared with the SD rats. After intratracheal instillation with the lower (5 x 10(3) L. monocytogenes) dose, pulmonary bacterial clearance was slowed and an increase in pulmonary responsiveness was observed for the F344 rats as compared to the SD rats. Specifically, the total number of neutrophils recovered from the lungs and tumor necrosis factor-alpha secreted by AMs were elevated for the F344 group throughout the 7 days, while cellular chemiluminescence, an index of reactive oxygen species production, and lung albumin and lactate dehydrogenase, indicators of injury, were increased at 3 and 5 days after bacterial instillation. This study demonstrated that respiratory defense function was compromised in F344 rats as evidenced by elevated mortality, slowed pulmonary bacterial clearance, and altered AM function. F344 rats may then represent a sensitive model for the examination of respiratory defense mechanisms after bacterial challenge.
