Role of lipoxygenase metabolites for the hyper-responsiveness to platelet-activating factor of lungs from actively sensitized guinea pigs.
The contribution of lipoxygenase metabolites to active sensitization-induced lung hyper-responsiveness in the guinea pig was investigated. Active sensitization was performed by two injections of 10 micrograms of ovalbumin in 1 mg of AI(OH)3 at a 2-week interval. The i.a. administration of increasing doses (1, 100 and 1000 ng) of platelet-activating factor (PAF-acether) into isolated perfused lungs from actively sensitized guinea pigs was followed by an enhanced bronchoconstriction as compared to that observed in lungs from nonimmunized animals. PAF-acether stimulation of actively sensitized lungs was accompanied by histamine secretion and by an increased release of leukotriene (LT)-like material (as detected by bioassay using guinea pig tracheal strips superfused with the lung effluent and by a radioimmunoassay for LTC4). Maximal PAF-acether-induced lung responses were observed 7 days after the booster injection of the antigen and remained at a plateau for at least 4 months. Lung response to antigen challenge occurred in parallel with the increase of the level of circulating immunoglobulin G and with the development of hyper-responsiveness up to 7 days after the booster injection. Then, a progressive decrease in the antigen-induced bronchoconstriction and mediator release was observed. Lungs from animals in which the booster injection was omitted responded to PAF-acether in a similar fashion as lungs from nonimmunized guinea pigs, even though they underwent anaphylactic reaction upon antigen challenge. Enhanced bronchoconstriction, tracheal contraction, immunoreactive LTC4-like material release, but not histamine secretion were suppressed by BW 755C, a mixed cyclooxygenase and lipoxygenase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
Pretolani
M
M
Unité de Pharmacologie Cellulaire/Unité Associée Institut Pasteur/Institut National de la Santé et de la Recherche Médicale No. 285, Paris, France.
Lefort
J
J
Dumarey
C
C
Vargaftig
B B
BB
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006636:Histamine Release; D007114:Immunization; D007136:Immunoglobulins / Q000097:blood; D007700:Kinetics; D008084:Lipoxygenase / Q000502:physiology*; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D013189:SRS-A / Q000032:analysis; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D007136:Immunoglobulins; D010972:Platelet Activating Factor; D011720:Pyrazoles; D013189:SRS-A; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D008084:Lipoxygenase