Arachidonic acid products and the thoracic accumulation of neutrophils and platelets following i.v. antigen challenge of sensitised guinea-pig.
The 5-lipoxygenase inhibitors, AA861 and phenidone, have been shown to inhibit the formation and release of leukotrienes C4, D4 and B4 from isolated perfused sensitised guinea pigs lungs when challenged through either the pulmonary system or the airways. The same drugs inhibit the thoracic neutrophil, but not platelet, accumulation observed following i.v. antigen challenge of sensitised guinea pigs. Indomethacin, a cyclooxygenase inhibitor, at doses which inhibited an arachidonic acid-induced thoracic platelet accumulation, had no effect on the platelet response following antigen challenge. Indomethacin did affect, however, the neutrophil response to antigen challenge presumably through mechanisms unrelated to cyclooxygenase inhibition. These observations suggest a role for lipoxygenase products, possibly LTB4, but not cyclooxygenase products in the neutrophil response to i.v. antigen challenge.
Walker
J R
JR
Lilly Research Centre Ltd, Eli Lilly & Co., Surrey, UK.
Woodhouse
S A
SA
D000818:Animals; D000941:Antigens / Q000276:immunology; D001095:Arachidonic Acids / Q000378:metabolism*; D016227:Benzoquinones; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology*; D006168:Guinea Pigs; D007114:Immunization; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology
D000941:Antigens; D001095:Arachidonic Acids; D016227:Benzoquinones; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D011809:Quinones; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C015429:phenidone; D007213:Indomethacin