Platelet-activating factor mediates the ozone-induced increase in airway microvascular leakage in guinea pigs.
In the present study, we asked whether platelet-activating factor (PAF) mediates the ozone-induced increase in airway microvascular leakage. To answer this question, we examined the effect of a PAF receptor antagonist on the ozone-induced increase in airway microvascular leakage quantified by the extravasation of Evans blue dye in the guinea pig trachea and main bronchi. Guinea pigs were pretreated with the PAF receptor antagonist, E6123 ((S)-(+)-6-(2-chlorophenyl)-3-cyclopropane-carbonyl-8,11-dimethyl-2,3,4, 5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2- f][1,2,4]triazolo[4,3-a][1,4]diazepine) (0.01, 0.1 and 1.0 mg/kg i.v.) and then exposed to 3 ppm ozone for 30 min. The PAF receptor antagonist significantly reduced the ozone-induced increase in microvascular leakage in a dose-dependent manner in both the trachea and main bronchi. Our results indicate that PAF mediates the ozone-induced increase in airway microvascular leakage. We therefore suggest that PAF may be involved in ozone-induced airway inflammation.
Kaneko
T
T
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Ikeda
H
H
Fu
L
L
Nishiyama
H
H
Okubo
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001980:Bronchi / Q000098:blood supply / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology*; D008297:Male; D010126:Ozone / Q000633:toxicity*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects*; D014132:Trachea / Q000098:blood supply / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D018836:Inflammation Mediators; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C068033:E 6123; D010126:Ozone