Involvement of leukotriene C4 in PAF-induced death in mice.
The role of leukotrienes (LTs) in the pathogenesis of platelet-activating factor (PAF)-induced death in mice was reinvestigated, since previously reported results are in conflict. A novel 5-lipoxygenase inhibitor, E6080, and a leukotriene antagonist, LY17883, protected mice from PAF-induced death in a dose-dependent manner, while the well-known 5-lipoxygenase inhibitor, AA861, was less effective than E6080. After the intravenous injection of PAF in mice, immunoreactive leukotriene C4 (i-LTC4), which was co-eluted with authentic LTC4 in HPLC, was significantly increased in bronchoalveolar lavage fluid (BALF). Oral administration of E6080 suppressed the increase in i-LTCM4. The results suggest that LTs may play an important role in PAF-induced lethality in mice.
Tsunoda
H
H
Inflammation and Allergy Research Unit, Eisai Research Laboratories, Ibaraki, Japan.
Abe
S
S
Sakuma
Y
Y
Katayama
S
S
Katayama
K
K
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D016859:Lipoxygenase Inhibitors; D008297:Male; D051379:Mice; D010972:Platelet Activating Factor / Q000633:toxicity*; D013189:SRS-A / Q000032:analysis / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D000098:Acetophenones; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D013189:SRS-A; D013777:Tetrazoles; D013844:Thiazoles; C064507:E 6080; C044660:LY 171883