[The role of lipid mediators in bronchial hyperresponsiveness and airway eosinophil accumulation induced by antigen challenge in guinea pigs].
The aim of this study was elucidate the role of lipid mediators in bronchial hyperresponsiveness (BHR) and airway eosinophil accumulation 24 hours after an antigen challenge in guinea pigs. Thromboxane (TX) A2 receptor antagonist, S-1452 (1, 10 mg/kg), cysteinyl leukotriene (cLT) receptor antagonist, ICI-198, 615 (0.5, 5 mg/kg), platelet activating factor (PAF) receptor antagonist, E-6123 (1, 10 micrograms/kg), and each vehicle were intraperitoneally given 1 h before and 11 h after an ovalbumin (OVA) challenge. BHR to inhaled methacholine was measured and then bronchoalveolar lavage (BAL) was performed 24 h after the OVA challenge. The three drugs significantly inhibited BHR to methacholine, dose dependently. S-1452 significantly inhibited total cell counts (TCC). ICI-198, 615 significantly reduced both TCC and eosinophil percentage, but E-6123 did not alter TCC and cell differentiation in BAL fluid. Therefore, these results clearly showed that lipid mediators were involved in antigen-induced BHR and suggested that TXA2 and cLT may contribute to the penetration of inflammatory cells through capillary wall, still more cLT is concerned eosinophil accumulation with cell specificity. PAF dose not take part in the penetration of inflammatory cells.
Tachibana
H
H
3rd Department of Internal Medicine, Kanazawa University School of Medicine.
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D004804:Eosinophils / Q000473:pathology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006168:Guinea Pigs; D007191:Indazoles / Q000494:pharmacology*; D020024:Leukotriene Antagonists; D008297:Male; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018077:Receptors, Leukotriene; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D007191:Indazoles; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D011448:Prostaglandin Antagonists; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018077:Receptors, Leukotriene; D017482:Receptors, Thromboxane; D014230:Triazoles; C039351:platelet activating factor receptor; C054217:ICI 198615; C056566:S 145; C068033:E 6123; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor