Ozone-induced pulmonary inflammation and epithelial proliferation are partially mediated by PAF.

Ozone (O3) exposure stimulates airway inflammation and epithelial sloughing in a number of species, including mice. Platelet-activating factor (PAF) is a lipid mediator released by activated mast cells, macrophages, and epithelial cells and causes pulmonary inflammation and hyperpermeability. We hypothesized that the activation of PAF receptors is central to the development of inflammation and epithelial injury induced by acute O3 exposure in mice. To test this hypothesis, O3-susceptible C57BL/6J mice were treated with a PAF-receptor antagonist, UK-74505, or vehicle either before or immediately after 3-h exposure to O3 (2 parts/million) or filtered air. Bronchoalveolar lavage (BAL) fluids were collected 6 and 24 h after exposure. Differential cell counts and protein content of the lavage were used as indicators of inflammation in the airways. O3-induced epithelial injury was assessed by light microscopy, and DNA synthesis in epithelium of terminal bronchioles was estimated by using a bromodeoxyuridine-labeling index. Intercellular adhesion molecule 1 (ICAM-1) expression was also examined in the lung by immunohistochemical localization. O3 caused significant increases in polymorphonuclear leukocytes and protein in the BAL fluid, increased pulmonary epithelial proliferation, and increased epithelial expression of ICAM-1 compared with air-exposed, vehicle-treated control mice. Relative to O3-exposed, vehicle-treated control mice, UK-74505 before exposure significantly (P < 0.05) decreased BAL protein, polymorphonuclear leukocytes, and epithelial cells. O3-induced inflammation was similarly attenuated in mice treated with UK-74505 after exposure. These experiments thus support the hypothesis that O3-induced airways inflammation and epithelial damage in mice are partially mediated by activation of PAF receptors, possibly through modulation of ICAM-1 expression.
AuthorsM Longphre, L Zhang, J R Harkema, S R Kleeberger
JournalJournal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 86 Issue 1 Pg. 341-9 (Jan 1999) ISSN: 8750-7587 [Print] UNITED STATES
PMID9887149 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Oxidants, Photochemical
  • Platelet Activating Factor
  • Platelet Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
  • Ozone
  • Animals
  • Bronchoalveolar Lavage Fluid (cytology)
  • Cell Division (drug effects)
  • Epithelial Cells (drug effects, physiology)
  • Lung (cytology, drug effects)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidants, Photochemical (toxicity)
  • Ozone (toxicity)
  • Platelet Activating Factor (pharmacology)
  • Platelet Membrane Glycoproteins (antagonists & inhibitors)
  • Pneumonia (chemically induced, pathology)
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled

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