Attenuation of ozone-induced airway permeability in rats by pretreatment with cyclophosphamide, FPL 55712, and indomethacin.
Exposure of rats to ozone (O3) produces an increase in airway permeability and a concomitant influx of polymorphonuclear leukocytes in the lung. These observations raise the possibility that the inflammatory cells play a role in the cellular injury and increased airway permeability after O3 exposure. This study was therefore designed to determine if the inflammatory cells or their products are essential for the O3 effect. In a series of experiments, rats were rendered leukopenic with cyclophosphamide, treated with leukotriene B4 (LTB4), or with the inhibitors of lipoxygenase or cyclooxygenase products of arachidonic acid, followed by exposure to O3. A 2-h exposure to 0.8 ppm O3 caused a significant increase in the flux of proteins and albumin in bronchoalveolar lavage (BAL) and elevated the transport of 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA) from trachea to blood. The treatment with cyclophosphamide caused a significant reduction in the circulating and pulmonary leukocytes and prevented an increase in tracheal mucosal permeability to 99mTc-DTPA and the protein and albumin flux in BAL. While the intratracheal instillation of LTB4 did not affect the permeability, tracheal permeability and albumin levels in BAL in rats treated with LTD4 antagonist FPL 55712 and exposed to O3 were lower than in the untreated O3-exposed rats. Pretreatment with indomethacin also prevented the O3 effects, as reflected by the decreased protein and albumin flux in BAL and 99mTc-DTPA transport from trachea to blood. These data show a reduction in the effect of O3 by agents that affect leukocytes or their products. The results support a mechanism of increased permeability that is dependent upon inflammatory cells and their products.
Bhalla
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Community and Environmental Medicine, University of California, Irvine 92717.
Daniels
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Luu
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D000418:Albumins / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002867:Chromones / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced; D007975:Leukotriene B4 / Q000633:toxicity; D008297:Male; D010126:Ozone / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010539:Permeability / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics; D014132:Trachea / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000418:Albumins; D001798:Blood Proteins; D002867:Chromones; D007975:Leukotriene B4; D010126:Ozone; D003520:Cyclophosphamide; C006312:FPL 55712; D016284:Technetium Tc 99m Pentetate; D007213:Indomethacin