Sin A Z, Roche E M, Togias A, Lichtenstein L M, Schroeder J T
Johns Hopkins Asthma & Allergy Center, Department of Medicine, Division of Clinical Immunology, Baltimore, MD 21224, USA.
J Allergy Clin Immunol. 2001 Sep;108(3):387-93. doi: 10.1067/mai.2001.117459.
Studies show that nerve growth factor (NGF) exhibits immunomodulatory activity. This neurotrophin is found at high levels in the serum of asthmatic individuals, is released during allergic reactions, and is reported to augment in vitro histamine and leukotriene C4 release by human basophils.
Because basophils represent a substantial source of IL-4 and IL-13, we tested the effects of NGF on the secretion of these cytokines by cells prepared from allergic subjects and cells prepared from nonallergic subjects.
Cytokine and histamine were measured in culture supernatants by ELISA and fluorimetry, respectively. Both real-time RT-PCR and conventional RT-PCR were used to measure IL-13 mRNA expression. NGF receptor expression was determined by 2-color flow cytometry.
Basophil suspensions from allergic subjects secreted some 2.5-fold greater levels of IL-13 when cultured with NGF than did cells prepared from normal control subjects. Flow cytometry revealed no significant differences in TrkA receptors on basophils to explain these findings. The levels of IL-13 secreted by the 2 groups of donors also differed when cells were activated with IL-3 but not when they were activated with anti-IgE antibody. Both NGF and IL-3 failed to induce IL-13 in cell cultures depleted of basophils, suggesting that the measurable IL-13 was indeed basophil-derived. Real-time RT-PCR showed an average induction of IL-13 message above medium control that was 4.3 (+/- 1.7)-fold with NGF and 8.9 (+/- 3.7)-fold with IL-3. Finally, NGF priming resulted in a remarkable enhancement of IL-13 induced by anti-IgE. This was significantly greater than the priming observed for either the IL-4 or histamine when this stimulus was used.
NGF (like IL-3) can both directly stimulate IL-13 secretion and modulate IgE-mediated responses in basophils. Its enhanced effect on cells from allergic individuals raises the importance of this cytokine in the pathogenesis of allergic disease.
研究表明神经生长因子（NGF）具有免疫调节活性。这种神经营养因子在哮喘患者血清中含量很高，在过敏反应期间释放，并且据报道可增强人嗜碱性粒细胞体外组胺和白三烯C4的释放。
由于嗜碱性粒细胞是IL-4和IL-13的重要来源，我们测试了NGF对过敏受试者和非过敏受试者细胞中这些细胞因子分泌的影响。
分别通过ELISA和荧光法测量培养上清液中的细胞因子和组胺。实时RT-PCR和传统RT-PCR均用于测量IL-13 mRNA表达。通过双色流式细胞术测定NGF受体表达。
与正常对照受试者制备的细胞相比，过敏受试者的嗜碱性粒细胞悬液在与NGF一起培养时分泌的IL-13水平约高2.5倍。流式细胞术显示嗜碱性粒细胞上的TrkA受体无显著差异来解释这些发现。当细胞用IL-3激活时，两组供体分泌的IL-13水平也不同，但用抗IgE抗体激活时则无差异。NGF和IL-3均未能在嗜碱性粒细胞缺失的细胞培养物中诱导IL-13，这表明可测量的IL-13确实来源于嗜碱性粒细胞。实时RT-PCR显示，与培养基对照相比，NGF平均诱导IL-13信息增加4.3（±1.7）倍，IL-3为8.9（±3.7）倍。最后，NGF预刺激导致抗IgE诱导的IL-13显著增强。这明显大于使用该刺激时观察到的IL-4或组胺的预刺激。
NGF（如IL-3）既能直接刺激IL-13分泌，又能调节嗜碱性粒细胞中IgE介导的反应。其对过敏个体细胞的增强作用提高了这种细胞因子在过敏性疾病发病机制中的重要性。
