REPEATED SUBACUTE OZONE EXPOSURE OF INBRED MICE - AIRWAY INFLAMMATIONAND VENTILATION

The present study was designed to assess the effects of repeated subac ute ozone (O-3) exposure on pulmonary inflammation and ventilation in two inbred strains of mice differentially susceptible to a single O-3 exposure. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) mice we re exposed to 0.3 ppm O-3 for 48 and 72 h and after 14 days recovery, both strains were reexposed. Airway inflammation and lung injury were assessed by counting inflammatory cells and measuring total protein co ntent and lactate dehydrogenase (LDH) activity in bronchoalveolar lava ge (BAL) returns. Minute ventilation [V-E, the product of breathing fr equency (f), and tidal volume (V-T)] was measured prior to and immedia tely following each exposure. After the initial exposure, B6 mice deve loped greater O-3-induced increases in total protein, inflammatory cel l influx, and LDH activity compared to C3 mice. In normal air, V-E, wa s also significantly elevated in B6, but not C3, mice after O-3. The h ypercapnic f of B6 and hypercapnic V-T of C3 mice were significantly a ltered after O-3 exposure. Reexposure to O-3 caused a smaller increase in the numbers of macrophages, lymphocytes, epithelial cells, and BAL protein in both strains, and no changes in LDH activity. However, the number of polymorphonuclear leukocytes significantly increased in B6 and C3 mice as compared to the initial O-3 exposure. In both strains, the ventilatory responses to normal air or hypercapnia were largely re producible after O-3 reexposure. Results indicated that differential s usceptibility to O-3-induced inflammation was maintained in B6 and C3 mice with O-3 reexposure although the magnitude of the difference was reduced. Results also suggest that the ventilatory responses to O-3 in B6 and C3 mice were reproducible with reexposure, and that airway inf lammation and ventilation were not codependent.