Repeated subacute ozone exposure of inbred mice: airway inflammation and ventilation.
The present study was designed to assess the effects of repeated subacute ozone (O3) exposure on pulmonary inflammation and ventilation in two inbred strains of mice differentially susceptible to a single O3 exposure. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) mice were exposed to 0.3 ppm O3 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 content and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage (BAL) returns. Minute ventilation [VE, the product of breathing frequency (f), and tidal volume (VT)] was measured prior to and immediately following each exposure. After the initial exposure, B6 mice developed greater O3-induced increases in total protein, inflammatory cell influx, and LDH activity compared to C3 mice. In normal air, VE was also significantly elevated in B6, but not C3, mice after O3. The hypercapnic f of B6 and hypercapnic VT of C3 mice were significantly altered after O3 exposure. Reexposure to O3 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 O3 exposure. In both strains, the ventilatory responses to normal air or hypercapnia were largely reproducible after O3 reexposure. Results indicated that differential susceptibility to O3-induced inflammation was maintained in B6 and C3 mice with O3 reexposure although the magnitude of the difference was reduced. Results also suggest that the ventilatory responses to O3 in B6 and C3 mice were reproducible with reexposure, and that airway inflammation and ventilation were not codependent.
Paquette
N C
NC
Department of Environmental Health Sciences, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 21205.
Tankersley
C G
CG
Zhang
L Y
LY
Kleeberger
S R
SR
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism; D012119:Respiration / Q000187:drug effects*; D013045:Species Specificity; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors
D011506:Proteins; D010126:Ozone; D007770:L-Lactate Dehydrogenase