Attenuation of ozone-induced airway permeability in rats by pretreatment with cyclophosphamide, FPL 55712, and indomethacin

Journal Article · Wed Jul 01 00:00:00 EDT 1992 · American Journal of Respiratory Cell and Molecular Biology; (United States)

DOI:https://doi.org/10.1165/ajrcmb/7.1.73· OSTI ID:7107144

Bhalla, D K; Daniels, D S; Luu, N T ^[1]

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1. Community and Environmental Medicine, University of California, Irvine (United States)

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.

• OSTI ID: 7107144
• Journal Information: American Journal of Respiratory Cell and Molecular Biology; (United States), Vol. 7:1; ISSN 1044-1549
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ENDOXAN
BIOLOGICAL EFFECTS
ENZYME INHIBITORS
LUNGS
SENSITIVITY
OZONE
TOXICITY
ALBUMINS
DTPA
ISOMERIC NUCLEI
LAVAGE
LEUKOCYTES
LEUKOPENIA
PERMEABILITY
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TECHNETIUM 99
ALKYLATING AGENTS
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CHELATING AGENTS
DISEASES
DRUGS
HEMIC DISEASES
HOURS LIVING RADIOISOTOPES
IMMUNE SYSTEM DISEASES
IMMUNOSUPPRESSIVE DRUGS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MATERIALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RESPIRATORY SYSTEM
RODENTS
TECHNETIUM ISOTOPES
VERTEBRATES
YEARS LIVING RADIOI
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