Cheng J B, Pillar J, Conklyn M, Breslow R, Shirley J, Showell H J
Department of Immunology and Infectious Diseases, Pfizer Inc., Groton, CT 06340.
Adv Prostaglandin Thromboxane Leukot Res. 1989;19:187-90.
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.
在体外抗原攻击时，来自IgG1致敏豚鼠的肺脏会合成白三烯（LTs）和血栓素（Tx）。本研究旨在调查抗原依赖性Tx合成是否可能源于之前LTD4的形成。在IgG1致敏的肺脏中，LTD4可有效诱导Tx形成（半数有效剂量[ED50]=2 - 4 nM）。在这些肺脏中，LTD4抗原依赖性形成的水平（由0.01 - 10微克/毫升抗原攻击形成8 - 26 nM）比LTD4刺激Tx合成的ED50值高2 - 7倍。此外，在抗原攻击前，用LTD4拮抗剂ICI - 198,615孵育致敏肺脏可阻止Tx形成（半数抑制浓度[IC50]=0.01 microM）。我们的结果表明，由IgG1致敏肺脏产生的LTD4可能在刺激Tx合成中起重要作用。由于抗原刺激后LTC4的快速形成及其诱导Tx合成的能力，LTC4可能也参与其中。
