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)