Human basophils secrete IL-3: evidence of autocrine priming for phenotypic and functional responses in allergic disease.
Human basophils secrete IL-3: evidence of autocrine priming for phenotypic and functional responses in allergic disease.
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DOI：
10.4049/jimmunol.0801782
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发表时间：
2009-02-15
期刊：
影响因子：
--
通讯作者：
Bieneman AP
中科院分区：
文献类型：
--
作者：
Schroeder JT;Chichester KL;Bieneman AP
虽然IL-3通常被认为具有生长因子样活性，但体外研究早已证明这种细胞因子也具有增强人嗜碱性粒细胞的促炎特性和表型的独特能力。特别是，嗜碱性粒细胞分泌的介质是过敏性疾病的标志，包括血管活性胺（如组胺），脂质代谢物（如LTC 4）和细胞因子（如IL-4/IL-13），这都是显著增强与IL-3预处理。这种引发现象在响应IgE依赖性和IgE非依赖性刺激时观察到。此外，IL-3直接激活嗜碱性粒细胞分泌IL-13和增强CD 69表达-这两种标志物在过敏受试者中升高。淋巴细胞通常被认为是IL-3的来源，其引发这些嗜碱性粒细胞应答。然而，我们在这里首次证明，嗜碱性粒细胞本身迅速产生IL-3（4小时内）响应IgE依赖性激活。更重要的是，我们的研究结果明确表明，嗜碱性粒细胞迅速结合并利用它们产生的IL-3，如在中和抗IL-3受体（CD 123）Ab存在下被抑制的功能和表型活性所证明的。我们预测，特异性过敏原引起的低水平IgE/FcεRI交联导致的自分泌IL-3活性代表了在过敏性疾病中长期观察到的嗜碱性粒细胞高反应性背后的重要机制。
Although IL-3 is commonly recognized for its growth factor-like activity, in vitro studies have long demonstrated a unique capacity for this cytokine to also augment the pro-inflammatory properties and phenotype of human basophils. In particular, basophils secrete mediators that are hallmark in allergic disease including vasoactive amines (e.g. histamine), lipid metabolites (e.g. LTC4) and cytokines (e.g. IL-4/IL-13), which are all markedly enhanced with IL-3 pretreatment. This priming phenomenon is observed in response to both IgE-dependent and IgE-independent stimulation. In addition, IL-3 directly activates basophils for IL-13 secretion and enhanced CD69 expression –two markers that are elevated in allergic subjects. Lymphocytes are commonly thought to be the source of the IL-3 that primes for these basophil responses. However, we demonstrate here for the first time that basophils themselves rapidly produce IL-3 (within 4h) in response to IgE-dependent activation. More importantly, our findings definitively show that basophils rapidly bind and utilize the IL-3 they produce, as evidenced by functional and phenotypic activity that is inhibited in the presence of neutralizing anti-IL-3 receptor (CD123) Ab. We predict that autocrine IL-3 activity resulting from low-level IgE/FcεRI cross-linking by specific allergen represents an important mechanism behind the hyper-reactive nature of basophils that has long been observed in allergic disease.
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