Theoharides Theoharis C, Kempuraj Duraisamy, Tagen Michael, Conti Pio, Kalogeromitros Dimitris
Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts - New England Medical Center, Boston, MA, USA.
Immunol Rev. 2007 Jun;217:65-78. doi: 10.1111/j.1600-065X.2007.00519.x.
Mast cells are well known for their involvement in allergic and anaphylactic reactions, during which immunoglobulin E (IgE) receptor (Fc epsilon RI) aggregation leads to exocytosis of the content of secretory granules (1000 nm), commonly known as degranulation, and secretion of multiple mediators. Recent findings implicate mast cells also in inflammatory diseases, such as multiple sclerosis, where mast cells appear to be intact by light microscopy. Mast cells can be activated by bacterial or viral antigens, cytokines, growth factors, and hormones, leading to differential release of distinct mediators without degranulation. This process appears to involve de novo synthesis of mediators, such as interleukin-6 and vascular endothelial growth factor, with release through secretory vesicles (50 nm), similar to those in synaptic transmission. Moreover, the signal transduction steps necessary for this process appear to be largely distinct from those known in Fc epsilon RI-dependent degranulation. How these differential mast cell responses are controlled is still unresolved. No clinically available pharmacological agents can inhibit either degranulation or mast cell mediator release. Understanding this process could help develop mast cell inhibitors of selective mediator release with novel therapeutic applications.
肥大细胞因其参与过敏和过敏反应而广为人知，在此过程中，免疫球蛋白E（IgE）受体（FcεRI）聚集会导致分泌颗粒（1000纳米）内容物的胞吐作用，即通常所说的脱颗粒，并分泌多种介质。最近的研究结果表明，肥大细胞也参与炎症性疾病，如多发性硬化症，在光学显微镜下肥大细胞似乎完好无损。肥大细胞可被细菌或病毒抗原、细胞因子、生长因子和激素激活，导致不同介质的差异性释放而不发生脱颗粒。这一过程似乎涉及介质的从头合成，如白细胞介素-6和血管内皮生长因子，并通过分泌小泡（50纳米）释放，类似于突触传递中的小泡。此外，这一过程所需的信号转导步骤似乎与FcεRI依赖性脱颗粒中已知的步骤有很大不同。这些肥大细胞的差异性反应是如何被控制的仍未得到解决。目前临床上没有可用的药物能够抑制脱颗粒或肥大细胞介质释放。了解这一过程有助于开发具有新型治疗应用的选择性介质释放的肥大细胞抑制剂。
