Leukotriene production in human neutrophils primed by recombinant human granulocyte/macrophage colony-stimulating factor and stimulated with the complement component C5A and FMLP as second signals.
Leukotriene production in human neutrophils primed by recombinant human granulocyte/macrophage colony-stimulating factor and stimulated with the complement component C5A and FMLP as second signals.
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DOI：
10.1084/jem.167.4.1281
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发表时间：
1988-04-01
期刊：
影响因子：
--
通讯作者：
de Weck AL
中科院分区：
文献类型：
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作者：
Dahinden CA;Zingg J;Maly FE;de Weck AL
中性粒细胞（PMN）与重组人粒细胞/巨噬细胞集落刺激因子（rhGM-CSF）预孵育2 h，然后用趋化因子C5 a或FMLP刺激，产生大量的脂氧合酶产物5-Hete、LTB 4和ω-氧化的LTB 4代谢物（4.36 +/- 0.95（SEM）pM（n = 21）LTB 4和LTB 4代谢物/10（6）PMN）。如果纯化的PMN在没有外源性花生四烯酸的情况下被GM-CSF或趋化因子刺激，则HPLC和RIA检测不到脂氧合酶代谢产物。GM-CSF对趋化因子诱导的脂质介质产生的引发作用是一个相对缓慢的过程，在1小时后明显，2小时后最佳。用0.8 U GM-CSF/10（6）PMN可测量白三烯生成，用80 U（10（-11）-10（-9）M）可达到最大。在用趋化因子激活致敏的PMN后，非常迅速地诱导白三烯合成。在活化后2.5分钟，存在的主要脂氧合酶代谢物是20-OH LTB 4和20-COOH LTB 4。我们的研究表明，从内源性AA的脂氧合酶代谢产物的合成可以启动在中性粒细胞通过受体介导的过程，由生物可溶性炎症介质肽的适当定时组合。此外，这些结果表明，GM-CSF不仅增强效应细胞的功能，但可以定性地改变后形成的第二触发信号激活后的介质分布。这种机制在放大炎症反应中可能很重要。另外，脂质介质形成也可能有细胞内或autocoid的作用，并负责增强其他PMN功能，如氧自由基释放。
Neutrophils (PMN) preincubated with recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) for 2 h and then stimulated with the chemotactic factors, C5a or FMLP, produce substantial amounts of the lipoxygenase products 5-Hete, LTB4, and omega-oxidised LTB4 metabolites (4.36 +/- 0.95 (SEM) pM (n = 21) LTB4 and LTB4 metabolites/10(6) PMN). No lipoxygenase metabolites are detected by HPLC and RIA if purified PMN are stimulated by either GM- CSF or chemotactic factors in the absence of exogenous arachidonate. The priming effect of GM-CSF upon chemotactic factor induced generation of lipid mediators is a relatively slow process, clearly evident after 1 h and optimal after 2 h. Leukotriene generation is measurable with 0.8 U GM-CSF/10(6) PMN and is maximal with 80 U (10(-11)-10(-9) M). Upon activation of primed PMN with chemotactic factors, leukotriene synthesis is induced very rapidly. Already 2.5 min after activation the major lipoxygenase metabolites present are 20-OH LTB4 and 20-COOH LTB4. Our study shows that the synthesis of lipoxygenase metabolites from endogeneous AA can be initiated in PMN through receptor mediated processes by the appropriately timed combination of biological soluble inflammatory mediator peptides. Furthermore, these results indicate that GM-CSF not only enhances effector cell functions but can qualitatively change the mediator profile formed after activation with a second triggering signal. Such a mechanism might be important in amplifying inflammatory responses. Alternatively, lipid mediators formed might also have an intracellular or autocoid role and be responsible for the enhancement of other PMN functions like oxygen radical release.