Benatuil Lorenzo, Apitz-Castro Rafael, Romano Egidio
Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Laboratorio de Trombosis Experimental, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas - IVIC, Caracas 1020-A, Venezuela.
Xenotransplantation. 2003 Jul;10(4):368-73. doi: 10.1034/j.1399-3089.2003.02016.x.
Ajoene, is an organosulfur compound derived from garlic that strongly inhibit platelet aggregation, proliferation of human lymphocytes induced by phytohemagglutinin, and in general, blocks membrane-mediated signaling of cell activation. As a thrombotic microangiopathy frequently complicates procedures designed to induce pig-to-baboon chimerism by infusion of large amounts of pig progenitor cells in baboons, it was thought that ajoene might be useful to prevent such complication. For such purpose, we studied the effects of ajoene on the activation of human umbilical vein endothelial cells (HUVEC) induced by pig peripheral blood mononuclear cells (p-PBMC). Co-cultures of p-PBMC with HUVEC results in activation of the HUVEC as shown by over-expression of E-selectin and vascular cells adhesion molecule-1 (VCAM-1). Ajoene (25 microm) strongly inhibits HUVEC activation induced by tumor necrosis factor-alpha (TNF-alpha) or p-PBMC as shown by a down regulation of VCAM-1 and of E-selectin expression. After 5 or 8 h of pre-treatment with Ajoene, HUVEC incubated with TNF and p-PBMC showed an E-selectin or VCAM-1 expression, respectively, at levels similar to the positive control indicating that the inhibitory effect is transient. Ajoene at concentration of 25 microm or lower did not affect HUVEC viability. Based on the finding that Ajoene has a strong, although transient, inhibitory effect on the activation of the endothelium induced by pig cells and its known anti-platelet activity, it is suggested that this garlic compound could be useful to prevent the development of microangiopathy and thrombotic disorders seen in primates infused with pig cells.
阿霍烯是一种从大蒜中提取的有机硫化合物，它能强烈抑制血小板聚集、植物血凝素诱导的人淋巴细胞增殖，并且一般会阻断细胞活化的膜介导信号传导。由于血栓性微血管病常常使通过向狒狒输注大量猪祖细胞来诱导猪 - 狒狒嵌合体的程序变得复杂，因此人们认为阿霍烯可能有助于预防这种并发症。出于这个目的，我们研究了阿霍烯对猪外周血单个核细胞（p - PBMC）诱导的人脐静脉内皮细胞（HUVEC）活化的影响。p - PBMC与HUVEC共培养会导致HUVEC活化，这通过E - 选择素和血管细胞粘附分子 - 1（VCAM - 1）的过度表达得以体现。阿霍烯（25微摩尔）强烈抑制肿瘤坏死因子 - α（TNF - α）或p - PBMC诱导的HUVEC活化，这通过VCAM - 1和E - 选择素表达的下调得以显示。用阿霍烯预处理5或8小时后，与TNF和p - PBMC一起孵育的HUVEC分别显示出E - 选择素或VCAM - 1表达，其水平与阳性对照相似，表明这种抑制作用是短暂的。浓度为25微摩尔或更低的阿霍烯不会影响HUVEC的活力。基于阿霍烯对猪细胞诱导的内皮细胞活化具有强烈（尽管是短暂的）抑制作用及其已知的抗血小板活性这一发现，有人提出这种大蒜化合物可能有助于预防在输注猪细胞的灵长类动物中出现的微血管病和血栓性疾病的发展。
