Corticotropin-releasing hormone and its structurally related urocortin are synthesized and secreted by human mast cells
Corticotropin-releasing hormone and its structurally related urocortin are synthesized and secreted by human mast cells
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DOI：
10.1210/en.2003-0805
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
Theoharides, TC
中科院分区：
文献类型：
--
作者：
Kempuraj, D;Papadopoulou, NG;Theoharides, TC
应激通过CRH激活下丘脑-垂体-肾上腺轴，导致糖皮质激素的产生，从而下调免疫反应。然而，急性应激也具有促炎作用。我们以前发现，束缚应激，以及CRH和其结构相关的尿皮质素（UCN），可以激活肥大细胞和触发肥大细胞依赖的血管通透性。在这里，我们首次表明，人脐带血来源的培养肥大细胞（hCBMC）在10周，但不是在2周，免疫细胞化学阳性CRH和UCN;人白血病肥大细胞弱阳性的两种肽。这些肥大细胞合成CRH和Ucn的能力通过RT-PCR显示mRNA表达来证实。hCBMC（8-14周）合成并储存1-10 ng/10（6）细胞（10-20 μ g/g）CRH和Ucn，通过细胞匀浆ELISA检测。用抗IgE刺激IgE致敏的hCBMC导致大多数CRH和Ucn的分泌。这些发现表明肥大细胞不仅是CRH和UCN的靶点，而且是CRH和UCN的潜在来源，CRH和UCN可能具有自分泌和旁分泌功能，特别是在应激加剧的过敏性炎症性疾病中。
Stress activates the hypothalamic-pituitary-adrenal axis through CRH, leading to production of glucocorticoids that down-regulate immune responses. However, acute stress also has proinflammatory effects. We previously showed that restraint stress, as well as CRH and its structurally related urocortin (Ucn), could activate mast cells and trigger mast cell-dependent vascular permeability. Here we show for the first time that human cord blood-derived cultured mast cells (hCBMC) at 10 wk, but not at 2 wk, are immunocytochemically positive for CRH and Ucn; human leukemic mast cells are weakly positive for both peptides. The ability of these mast cells to synthesize CRH and Ucn was confirmed by showing mRNA expression with RT-PCR. hCBMC (8-14 wk) synthesize and store 1-10 ng/10(6) cells (10-20 mug/g) of both CRH and Ucn detected by ELISA of cell homogenates. Stimulation of IgE-sensitized hCBMC with anti-IgE results in secretion of most CRH and Ucn. These findings indicate that mast cells are not only the target, but also a potential source of CRH and Ucn that could have both autocrine and paracrine functions, especially in allergic inflammatory disorders exacerbated by stress.