INTERLEUKIN-3 AND GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR RENDER HUMAN BASOPHILS RESPONSIVE TO LOW CONCENTRATIONS OF COMPLEMENT COMPONENT-C3A
INTERLEUKIN-3 AND GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR RENDER HUMAN BASOPHILS RESPONSIVE TO LOW CONCENTRATIONS OF COMPLEMENT COMPONENT-C3A
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DOI：
10.1073/pnas.87.17.6813
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发表时间：
1990-09-01
影响因子：
11.1
通讯作者：
DAHINDEN, CA
中科院分区：
文献类型：
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作者：
BISCHOFF, SC;DEWECK, AL;DAHINDEN, CA
补体成分C3a是一种已知能诱导血浆渗出和组织平滑肌收缩的过敏毒素。然而，对炎症效应白细胞的影响是不明确的和有争议的，充其量是微弱的，发生在非常高的C3a浓度。在这里，我们研究了C3a对人嗜碱性细胞释放介质的影响，有和没有预处理白细胞介素3 (IL-3)，一种造血生长因子，最近发现可以深刻地改变嗜碱性细胞对各种细胞激动剂的反应。在没有细胞因子的情况下，C3a，即使浓度为1 μ。M，对嗜碱性粒细胞介质释放无效或仅微弱刺激。然而，当嗜碱性细胞用浓度仅为0.01-1单位/ml的IL-3预处理时，它们对C3a产生反应，释放大量组胺，并产生白三烯。令人惊讶的是，即使是非常低的C3a浓度（1 nM）也能产生几乎最佳的效果。另一种造血生长因子，粒细胞/巨噬细胞集落刺激因子（GM-CSF）也被发现使嗜碱性细胞能够对C3a产生反应，但其作用弱于IL-3。c3a诱导的组胺释放和白三烯生成在il -3引物细胞中迅速发生，分别在0.5 min和2 min后完成。在非常低浓度的C3a下出现快速而强烈的脱颗粒反应，表明嗜碱性细胞上存在高亲和力的C3a受体，这可能是由细胞因子诱导的。我们的研究结果表明，依赖于IL-3或GM-CSF的存在，C3a是一种有效的嗜碱性粒细胞激活剂，这种现象可能与各种炎症过程有关，特别是超敏反应。
Complement component C3a is an anaphylatoxin known to induce plasma exudation and smooth muscle contraction in tissues. The effects on inflammatory effector leukocytes, however, are poorly defined and controversial, being at best weak and occurring at very high C3a concentrations. Here, we examined the effect of C3a upon mediator release from human basophils, with and without pretreatment with interleukin 3 (IL-3), a hematopoietic growth factor recently found to profoundly modify the basophil response to various cell agonists. In the absence of cytokines, C3a, even at a concentration of 1 .mu.M, was ineffective or only weakly stimulatory for basophil mediator release. However, when basophils were pretreated with IL-3 at concentration of only 0.01-1 unit/ml, they became responsive to C3a, releasing large amounts of histamine and also generating leukotrienes. Surprisingly, almost optimal effects occurred with even very low C3a concentrations (1 nM). Another hematopoietic growth factor, granulocyte/macrophage-colony-stimulating factor (GM-CSF), was also found to render basophils capable of responding to C3a, but the effect was weaker than that of IL-3. C3a-induced histamine release and leukotriene generation occurred rapidly in IL-3-primed cells, being complete after 0.5 and 2 min, respectively. The rapid and strong degranulation response, occurring at very loow concentrations of C3a, suggests the presence of a high-affinity C3a receptor on basophils, which might be inducible by cytokines. Our results demonstrate that, depending on the presence of IL-3 or GM-CSF, C3a is a potent basophil activator, and such a phenomenon could be of relevance in various inflammatory processes, especially hypersensitivity reactions.