Brunner T, de Weck A L, Dahinden C A
Institute of Clinical Immunology, Inselspital, Bern, Switzerland.
J Immunol. 1991 Jul 1;147(1):237-42.
The phospholipid platelet-activating factor (PAF) is a potent cell-derived bioactive molecule thought to be involved in diverse inflammatory processes. It has been shown that PAF can activate different leukocyte types and platelets, particularly in synergy with other agonists. In this study we examined the effect of PAF upon the release of histamine and leukotriene (LT) C4 by basophils when added alone and in combination with different agonists and cytokines. PAF by itself did neither induce histamine release nor the generation of LTC4 by basophils. However, basophils primed by the hematopoietic growth factors (hGF) IL-3, granulocyte-macrophage (GM)-CSF, or IL-5 (10 ng/ml) released preformed and de novo synthesized mediators in response to PAF at 10 to 100 nM concentrations. The extent of mediator release by hGF primed basophils in response to PAF was similar to that induced by an optimal concentration of monoclonal anti-IgE. Thus, similar to NAP-1/IL-8 and C3a, PAF efficiently stimulates mediator release in hGF-primed basophils only. However, PAF was clearly a more potent trigger of LTC4 formation in IL-3-primed cells than NAP-1/IL-8 or C3a. When PAF was used as a second trigger, the priming effect of IL-5 was less than that of IL-3 or GM-CSF, whereas the response for other IgE-independent agonists (i.e., C5a or FMLP) was augmented equally by all three hGF. IL-1 beta-pretreated basophils released minimal amounts of histamine in response to PAF. Neither TNF-alpha nor PAF, nor the combination thereof, was able to induce basophil mediator release. The efficiency of the different cytokines to prime for PAF responsiveness was strikingly similar to their capacity to enhance anti-IgE-induced mediator release. Similar to other IgE-independent agonists, the kinetic of mediator release in response to PAF was very rapid. PAF pretreatment of basophils did not enhance mediator release in response to diverse agonists, such as C5a and FMLP, in contrast to the capacity of PAF to augment the response of other leukocyte types to appropriate stimuli. Thus, depending on the presence of IL-3, GM-CSF, or IL-5, PAF is a potent basophil agonist capable of inducing histamine release as well as de novo synthesis of LTC4.
磷脂血小板活化因子（PAF）是一种强大的细胞源性生物活性分子，被认为参与多种炎症过程。研究表明，PAF可激活不同类型的白细胞和血小板，尤其是与其他激动剂协同作用时。在本研究中，我们考察了单独添加PAF以及将其与不同激动剂和细胞因子联合添加时，PAF对嗜碱性粒细胞释放组胺和白三烯（LT）C4的影响。单独的PAF既不诱导嗜碱性粒细胞释放组胺，也不诱导其生成LTC4。然而，经造血生长因子（hGF）白细胞介素-3（IL-3）、粒细胞-巨噬细胞（GM）-集落刺激因子（CSF）或IL-5（10纳克/毫升）预刺激的嗜碱性粒细胞，在10至100纳摩尔浓度的PAF作用下，会释放预先形成的和新合成的介质。hGF预刺激的嗜碱性粒细胞对PAF的介质释放程度与最佳浓度的单克隆抗IgE诱导的程度相似。因此，与中性粒细胞激活蛋白-1/白细胞介素-8（NAP-1/IL-8）和C3a类似，PAF仅能有效刺激hGF预刺激的嗜碱性粒细胞释放介质。然而，在IL-3预刺激的细胞中，PAF显然是比NAP-1/IL-8或C3a更有效的LTC4形成触发因子。当将PAF用作二次触发因子时，IL-5的预刺激作用小于IL-3或GM-CSF，而对于其他非IgE依赖性激动剂（即C5a或N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）），这三种hGF对其反应的增强作用相同。白细胞介素-1β（IL-1β）预处理的嗜碱性粒细胞对PAF的反应释放的组胺量极少。肿瘤坏死因子-α（TNF-α）、PAF及其组合均不能诱导嗜碱性粒细胞释放介质。不同细胞因子引发PAF反应性的效率与其增强抗IgE诱导的介质释放的能力惊人地相似。与其他非IgE依赖性激动剂类似，嗜碱性粒细胞对PAF反应的介质释放动力学非常迅速。与PAF增强其他白细胞类型对适当刺激的反应能力相反，PAF预处理嗜碱性粒细胞不会增强其对多种激动剂（如C5a和FMLP）的介质释放。因此，取决于IL-3、GM-CSF或IL-5的存在情况，PAF是一种强大的嗜碱性粒细胞激动剂，能够诱导组胺释放以及LTC4的从头合成。
