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Inhibition of antigen-induced airway hyperresponsiveness, but not acute hypoxia nor airway eosinophilia, by an antagonist of platelet-activating factor.

Abstract
The role of platelet-activating factor (PAF) in Ag-induced airway hyperresponsiveness was evaluated in a guinea pig model using the PAF antagonist SDZ 64-412. Repeated OVA challenge by aerosol (twice weekly x 4 wk) of previously sensitized guinea pigs produced striking airway hyperresponsiveness as determined by pulmonary resistance changes to increasing doses of inhaled acetylcholine given 3 days after the last OVA challenge. Each OVA challenge produced significant hypoxia that was unaffected by oral pretreatment with 20 mg/kg SDZ 64-412, 2 h before each challenge (pO2 = 35 +/- 2 mm Hg for OVA alone vs 40 +/- 6 mm Hg for SDZ and OVA groups, respectively). SDZ 64-412 pretreatment abolished the airway hyperresponsiveness resulting from repeated Ag challenge. Morphometric analysis revealed that SDZ 64-412 treatment had no effect on the increased numbers of eosinophils that infiltrated the airways of OVA-challenged guinea pigs. These results suggest that PAF may be a primary mediator of airway hyperresponsiveness, but not acute bronchoconstriction, induced by repeated Ag challenge. This activity of PAF appears independent of eosinophil recruitment to airways.
AuthorsK Ishida, R J Thomson, L L Beattie, B Wiggs, R R Schellenberg
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 144 Issue 10 Pg. 3907-11 (May 15 1990) ISSN: 0022-1767 [Print] United States
PMID2332636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Isoquinolines
  • Platelet Activating Factor
  • SDZ 64-412
  • Ovalbumin
  • Acetylcholine
Topics
  • Acetylcholine (immunology)
  • Airway Resistance
  • Animals
  • Bronchial Provocation Tests
  • Bronchial Spasm (physiopathology)
  • Connective Tissue Cells
  • Eosinophils (immunology)
  • Epithelial Cells
  • Guinea Pigs
  • Hypersensitivity (physiopathology)
  • Isoquinolines (pharmacology)
  • Ovalbumin (immunology)
  • Platelet Activating Factor (antagonists & inhibitors)
  • Platelet Aggregation
  • Respiratory System (cytology)

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