In vivo priming of FcalphaR functioning on eosinophils of allergic asthmatics.
In vivo priming of FcalphaR functioning on eosinophils of allergic asthmatics.
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发表时间：
2000
影响因子：
5.5
通讯作者：
M. Bracke;E. A. van de Graaf;J. Lammers;P. Coffer;L. Koenderman
中科院分区：
文献类型：
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作者：
M. Bracke;E. A. van de Graaf;J. Lammers;P. Coffer;L. Koenderman
过敏性哮喘炎症的特点是嗜酸性粒细胞的涌入和支气管组织中嗜酸性粒细胞产物的存在。这种炎症反应的协调部分是由细胞因子和化学引诱剂介导的，但最终的激活可能需要额外的刺激。IgA是粘膜表面最丰富的免疫球蛋白，是嗜酸性粒细胞激活的潜在有效触发因子。先前，我们已经证明结合iga包被的靶标依赖于细胞因子的体外刺激。在这里，我们证明从过敏性哮喘患者血液中分离的嗜酸性粒细胞独立于先前的体外刺激结合IgA珠。此外，我们发现促炎细胞因子tnf - α是过敏性哮喘患者嗜酸性粒细胞与IgA结合的有效增强因子，并且它不会激活从正常供体分离的嗜酸性粒细胞上的FcalphaR。FcalphaRs在正常和患者嗜酸性粒细胞上结合IgA的差异可能与不同信号转导途径的激活有关。研究细胞内信号，我们发现来自过敏性哮喘患者的嗜酸性粒细胞中磷脂酰肌醇3-激酶（PI3K）的基础活性增强。此外，在这些细胞中抑制PI3K完全阻断了背景和tnf α诱导的IgA结合。总之，这些数据表明，人类嗜酸性粒细胞对tnf - α的反应性可能是微调过敏性炎症反应的重要贡献。此外，PI3K的预激活导致对炎症细胞因子的后续挑战具有更广泛的敏感性。
Inflammation in allergic asthma is characterized by an influx of eosinophils and the presence of eosinophil products in the bronchial tissue. Orchestration of this inflammatory response is in part mediated by cytokines and chemoattractants, but final activation can require additional stimuli. IgA, the most abundant immunoglobulin at mucosal surfaces, is potentially a potent trigger for eosinophil activation. Previously, we have shown that binding IgA-coated targets is dependent on in vitro stimulation of cells with cytokines. Here, we demonstrate that eosinophils isolated from the blood of allergic asthmatic patients bind IgA beads independently of prior in vitro stimulation. Furthermore, we found that the proinflammatory cytokine, TNF-alpha, is a potent enhancer of IgA binding to eosinophils from allergic asthmatics, and it does not activate FcalphaR on eosinophils isolated from normal donors. The difference in IgA binding by FcalphaRs on normal and patient eosinophils might be explained by the activation of different signal transduction pathways. Studying intracellular signaling, we found an enhanced basal activity of phosphatidylinositol 3-kinase (PI3K) in eosinophils derived from allergic asthmatics. Moreover, inhibition of PI3K in these cells blocked the background and the TNF-alpha-induced IgA binding completely. In summary, these data demonstrate that the responsiveness of human eosinophils to TNF-alpha might be an important contribution for fine-tuning the allergic inflammatory reaction. Furthermore, the preactivation of PI3K results in a broader sensitivity to subsequent challenge with inflammatory cytokines.