Gibbs Bernhard F, Zillikens Detlef, Grabbe Jürgen
Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Int Immunopharmacol. 2005 Apr;5(4):735-47. doi: 10.1016/j.intimp.2004.12.004.
NGF and IL-3 play a unique role in supporting human basophil differentiation and mediator secretion. Their importance in allergic disease is underlined further by studies showing elevated levels of these factors in asthmatics. Here, we compared the abilities of IL-3 and NGF to stimulate basophil histamine, IL-4 or IL-13 release, either directly or in conjunction with IgE-dependent stimulation and assessed the intracellular signals responsible. Our results show that the ability of IL-3 and NGF to enhance IgE-dependent histamine release are similar. Both factors also potentiated IgE-dependent IL-13 secretion to a greater degree than the release of histamine or IL-4. At high concentrations (100 ng/ml), IL-3 and NGF alone were capable of releasing cytokines but little histamine. These abilities of IL-3 and NGF to modulate basophil activation were sensitive to blockade by specific inhibitors of PI 3-kinase, p38 MAPK and PLC, but not PKC, suggesting that their effects are mediated considerably by pathways comparable to IgE-dependent signalling.
神经生长因子（NGF）和白细胞介素-3（IL-3）在支持人类嗜碱性粒细胞分化和介质分泌方面发挥着独特作用。哮喘患者体内这些因子水平升高的研究进一步凸显了它们在过敏性疾病中的重要性。在此，我们比较了IL-3和NGF直接或与IgE依赖性刺激联合刺激嗜碱性粒细胞释放组胺、IL-4或IL-13的能力，并评估了相关的细胞内信号。我们的结果表明，IL-3和NGF增强IgE依赖性组胺释放的能力相似。这两种因子增强IgE依赖性IL-13分泌的程度也高于组胺或IL-4的释放。在高浓度（100 ng/ml）时，单独的IL-3和NGF能够释放细胞因子，但组胺释放较少。IL-3和NGF调节嗜碱性粒细胞活化的这些能力对PI 3激酶、p38丝裂原活化蛋白激酶（MAPK）和磷脂酶C（PLC）的特异性抑制剂阻断敏感，但对蛋白激酶C（PKC）不敏感，这表明它们的作用在很大程度上是由与IgE依赖性信号传导相当的途径介导的。
