Mercury induces inflammatory mediator release from human mast cells.
Mercury induces inflammatory mediator release from human mast cells.
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DOI：
10.1186/1742-2094-7-20
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发表时间：
2010-03-11
影响因子：
9.3
通讯作者：
Theoharides TC
中科院分区：
文献类型：
--
作者：
Kempuraj D;Asadi S;Zhang B;Manola A;Hogan J;Peterson E;Theoharides TC
众所周知，汞具有神经毒性，但它对免疫系统的影响却鲜为人知。肥大细胞参与过敏反应，但也参与先天和后天免疫，以及炎症。许多患有自闭症谱系障碍(ASD)的患者都有“过敏”症状；此外，肥大细胞增多症患者的ASD患病率比一般人群高10倍，表明肥大细胞参与其中。因此，我们研究了氯化汞(HgCl2)对人肥大细胞激活的影响。用氯化汞(0.1~10μM)刺激培养的人白血病LAD2肥大细胞和正常脐血来源的肥大细胞10min，用ELISA法测定血管内皮生长因子和IL-6的释放。HgCl2诱导LAD2肥大细胞β-氨基己糖苷酶的释放增加2倍，0.1和1μM时分别为311±32pg/106cell和443±143pg/106cell，与对照组(227±17pg/106cell，n=5，p<；0.05)相比，差异有统计学意义。在促炎神经肽P物质(SP，0.1μM)中加入0.1μM的HgCl2对LAD 2肥大细胞的血管内皮生长因子有协同诱导作用。HgCl2还刺激人CBMCs释放血管内皮生长因子(360±100pg/106cell，1μM，n=5，p<；0.05)和IL-6释放(466±57pg/106cell，0.1μM，与未处理细胞(13±25pg/106cell，n=5，p<；0.05)。在SP(5μM)中加入HgCl2(0.1μM)进一步增加IL-6的释放。HgCl2刺激人肥大细胞释放血管内皮生长因子和IL-6。这种现象可能会破坏血脑屏障，导致脑部发炎。因此，本研究结果为低水平汞在ASD发病机制中的作用提供了生物学机制。
Mercury is known to be neurotoxic, but its effects on the immune system are less well known. Mast cells are involved in allergic reactions, but also in innate and acquired immunity, as well as in inflammation. Many patients with Autism Spectrum Disorders (ASD) have "allergic" symptoms; moreover, the prevalence of ASD in patients with mastocytosis, characterized by numerous hyperactive mast cells in most tissues, is 10-fold higher than the general population suggesting mast cell involvement. We, therefore, investigated the effect of mercuric chloride (HgCl2) on human mast cell activation. Human leukemic cultured LAD2 mast cells and normal human umbilical cord blood-derived cultured mast cells (hCBMCs) were stimulated by HgCl2 (0.1-10 μM) for either 10 min for beta-hexosaminidase release or 24 hr for measuring vascular endothelial growth factor (VEGF) and IL-6 release by ELISA. HgCl2 induced a 2-fold increase in β-hexosaminidase release, and also significant VEGF release at 0.1 and 1 μM (311 ± 32 pg/106 cells and 443 ± 143 pg/106 cells, respectively) from LAD2 mast cells compared to control cells (227 ± 17 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 μM) to the proinflammatory neuropeptide substance P (SP, 0.1 μM) had synergestic action in inducing VEGF from LAD2 mast cells. HgCl2 also stimulated significant VEGF release (360 ± 100 pg/106 cells at 1 μM, n = 5, p < 0.05) from hCBMCs compared to control cells (182 ± 57 pg/106 cells), and IL-6 release (466 ± 57 pg/106 cells at 0.1 μM) compared to untreated cells (13 ± 25 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 μM) to SP (5 μM) further increased IL-6 release. HgCl2 stimulates VEGF and IL-6 release from human mast cells. This phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis.
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DOI：
10.1080/15287390601172080
发表时间：
2007-01-01
影响因子：
2.6
作者：
Adams, James B.;Romdalvik, Jane;Legator, Marvin S.
通讯作者：
Legator, Marvin S.
影响因子：
56.9
作者：
Harris, HH;Pickering, IJ;George, GN
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1080/15287390701457712
发表时间：
2007-01-01
影响因子：
2.6
作者：
Geier, David A.;Geier, Mark R.
通讯作者：
Geier, Mark R.
影响因子：
10.4
作者：
Burbacher TM;Shen DD;Liberato N;Grant KS;Cernichiari E;Clarkson T
通讯作者：
Clarkson T