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Histological and molecular mechanisms of the permeability changes and inflammatory response in rat lungs following acute exposure to ozone

Thesis/Dissertation ·
OSTI ID:6973444
Time course experiments were conducted to investigate a possible relationship between two events known to exist following an acute O[sub 3] exposure: an increase in airway permeability and lung inflammation. The cytokine, tumor necrosis factor (TNF) may be a precursor to these events and therefore its presence and possible role in these events was also investigated. Albumin and total protein concentrations and the proportion of polymorphonuclear leukocytes (PMNs) in the bronchoalveolar lavage (BAL) were used as indicators of lung permeability and an inflammatory response. Albumin concentrations significantly increased from 2 to 8 hours, plateaued there until 16 hours, and then declined at 20 and 24 hours following a 3 hour exposure to 0.8 ppm O[sub 3]. Protein showed 2 to 3 fold increases at 2, 4 and 6 hours post-exposure. PMNs were less than 1% of the total cell population until 4 and 6 hours post-exposure when they increased to 3.38 and 4.49% respectively. TNF activity in BAL immediately following 0.8 ppm exposures for 0.5, 1, 2, and 3 hours and at 2, 4, and 6 hours post 3 hours exposure was similar to that in controls, i.e., <1 u/ml. Tracheal cross sections were stained with naphthol AS-D chloroacetate esterase and PMNs were scored by their location. The total PMN population remained at the control value up to 8 hours, increased at 12 hours, then declined. A shift in PMN location from vasculature to interstitium occurred at 8 hours post-exposure while stained PMNs increased at 16 hours post-exposure. The role of TNF in permeability increases and the inflammatory response was investigated by injecting, intraperitoneally, rabbit anti-mouse antibody of TNF-[alpha] (anti-TNF) before exposure. Albumin and total protein concentrations and the proportion of PMNs in BAL from the O[sub 3]-exposed anti-TNF pretreatment group showed an attenuating trend, but both O[sub 3]-exposed groups were significantly elevated in comparison to controls.
Research Organization:
California Univ., Irvine, CA (United States)
OSTI ID:
6973444
Country of Publication:
United States
Language:
English