Inhibition of antigen-induced airway hyperresponsiveness, but not acute hypoxia nor airway eosinophilia, by an antagonist of platelet-activating factor.
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.
Ishida
K
K
UBC Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Thomson
R J
RJ
Beattie
L L
LL
Wiggs
B
B
Schellenberg
R R
RR
D000109:Acetylcholine / Q000276:immunology; D000403:Airway Resistance; D000818:Animals; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000503:physiopathology*; D003239:Connective Tissue Cells; D004804:Eosinophils / Q000276:immunology; D004847:Epithelial Cells; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000503:physiopathology*; D007546:Isoquinolines / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation; D012137:Respiratory System / Q000166:cytology
D007546:Isoquinolines; D010972:Platelet Activating Factor; C057722:SDZ 64-412; D010047:Ovalbumin; D000109:Acetylcholine