The overall objective of this project is to develop an animal model of improved sensitivity for the detection of air-pollutant modulation of pulmonary host defense.
The specific aims are (1) to develop an optimal immunization schedule to modulate the pulmonary cellular response surrounding infected foci in rats chronically infected with Pseudomonas aeruginosa to increase the sensitivity in testing for air pollutant toxicity, (2) to test the sensitivity of this model using exposure to high and to ambient levels of NO2 as evaluated by: quantitation of bacterial numbers, pulmonary pathology and biochemical parameters of pulmonary lavage fluids. Rodent infectivity models have been extensively used in testing the effects of exposure to air pollutants on pulmonary susceptibility to bacterial infection. These studies have been performed with healthy animals while the human population most sensitive to pollutant-induced injury appears to be those persons suffering from chronic pulmonary disease. None of the animal models of chronic pulmonary bacterial infection has yet proven to have increased sensitivity over the standard infectivity assays performed with healthy animals. A modification of the P. aeruginosa agarose bead model using vaccinated rats indicates that the pulmonary lesion size may be controlled allowing increased sensitivity to air pollutant toxicity. Tests with this modified model are of potential value in assessing risk from pollutant exposure on persons suffering from chronic pulmonary disease as they appear to have an increased susceptibility to pollutant-induced injury.
