Species differences in release of arachidonate metabolites in response to inhaled diluted diesel exhaust.
In life-span studies in CD-1 mice and F344/Crl rats, inhaled diluted diesel exhaust was highly fibrogenic in rats but not in mice. This was the case despite the higher lung burden, in mg soot/g lung, achieved in mice compared to rats. We tested the hypothesis that the greater fibrogenicity of the soot in rats was due in part to greater release of mediators of inflammation from alveolar cells in rats compared to mice. Female F344/rats and B6C3F1 mice were exposed for up to 17 days to diluted diesel exhaust containing 3.5 mg/m3 of soot. The lungs of control and soot-exposed animals were lavaged after 2, 12 or 17 days of exposure. The presence of leukotriene (LT)B4, LTC4, prostaglandin (PG)E2, PGF2 alpha and thromboxane (TX) B2 in the lavage fluids and LTB4 and PGF2 alpha in cultured lavage cell supernatants was determined. The total amount of each lavage fluid constituent was normalized to lung weight for species comparisons. Control rats had higher levels of TXB2 (16-fold), and LTB4 (6-fold) and PGE2 (2-fold) than control mice, but control mice had higher amounts of LTC4 (4-fold). Control rats and mice had approximately the same amounts of PGF2 alpha/g lung in bronchoalveolar lavage fluid (BALF). Rats exposed to diesel exhaust had increases in BALF PGF2 alpha and LTB4 that were highest after 2 days of exposure and decreased thereafter. Mice had lesser increases in both parameters. Rat cells recovered from lavage fluid released larger amounts of LTB4 into culture supernatants than mouse cells. The data were consistent with the hypothesis that soot-laden rat alveolar cells release greater quantities of mediators of inflammation than do the alveolar cells in mice.
Henderson
R F
RF
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
Leung
H W
HW
Harmsen
A G
AG
McClellan
R O
RO
D000280:Administration, Inhalation; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D015232:Dinoprostone / Q000032:analysis; D007975:Leukotriene B4 / Q000032:analysis; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000032:analysis; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013929:Thromboxane B2 / Q000032:analysis; D001335:Vehicle Emissions / Q000633:toxicity*
D001095:Arachidonic Acids; D001335:Vehicle Emissions; D007975:Leukotriene B4; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015232:Dinoprostone