INVOLVEMENT OF PEPTIDOLEUKOTRIENES IN ANTIGEN-DEPENDENT THROMBOXANE (TX) SYNTHESIS IN IGG1-SENSITIZED GUINEA-PIG LUNGS

Lungs from IgG1-sensitized guinea pigs synthesize both leukotrienes (LTs) and thromboxane (Tx) upon ex vivo antigen challenge. This study was undertaken to investigate whether antigen-dependent Tx synthesis could result from prior formation of LTD4. In IgG1-sensitized lungs, LTD4 effectively induced Tx formation (ED50 = 2-4 nM). In these lungs, the levels of antigen-dependent formation of LTD4 (8-26 nM formed by 0.01-10 micrograms/ml antigen challenge) were 2-7 X greater than the ED50 value of LTD4-stimulated Tx synthesis. In addition, incubation of the sensitized lungs with ICI-198,615, a LTD4 antagonist, prior to antigen-challenge prevented Tx formation (IC50 = 0.01 microM). Our results indicate that LTD4 generated from IgG1-sensitized lungs could play a prominent role in stimulating Tx synthesis. LTC4 may also be involved because of rapid formation of LTC4 upon antigen-stimulation and its capacity to induce Tx synthesis.