Direct activation of porcine endothelial cells by human natural killer cells
Direct activation of porcine endothelial cells by human natural killer cells
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DOI：
10.1097/00007890-199603150-00016
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发表时间：
1996-03-15
期刊：
影响因子：
6.2
通讯作者：
Bach, FH
中科院分区：
文献类型：
--
作者：
Goodman, DJ;VonAlbertini, M;Bach, FH
内皮细胞（EC）活化是异种移植排斥反应的一致特征。用补体抑制剂和异种反应性天然抗体耗竭治疗异种移植物受体可导致延迟的异种移植物排斥反应，并伴有高达20%的自然杀伤（NK）细胞浸润。为了确定NK细胞在异种移植排斥反应中的重要性，我们在人Mt细胞和猪EC共培养中研究了EC的活化和细胞毒性。将新鲜分离的Mt细胞添加到猪EC中导致EC细胞活化，其特征是诱导粘附分子e -选择素和趋化细胞因子白细胞介素(IL)-8的mRNA和蛋白。e -选择素和IL-8的诱导发生在三种不同来源的NK细胞中：纯化的CD56+ve细胞、NK细胞克隆B22和Fc受体缺陷NK细胞系NK92。跨膨胀培养表明，EC诱导e -选择素和IL-8需要直接与NK-EC接触，这些作用不能被人重组肿瘤坏死因子α受体抑制，并且将活化EC的上清或细胞裂解物转移到二次培养中不会导致EC活化，添加人IgG可提高e -选择素的表达水平和细胞毒性。因此，人Mt细胞可以通过直接细胞接触裂解或激活EC， IgG的加入增强EC的激活和NK细胞细胞因子的分泌，这些发现提示NK细胞参与EC的激活和细胞介导的异种移植排斥反应。
Endothelial cell (EC) activation is a consistent feature of discordant xenograft rejection. Treatment of xenograft recipients with complement inhibitors and xenoreactive natural antibody depletion leads to delayed xenograft rejection associated with a cellular infiltrate comprising up to 20% natural killer (NK) cells. To determine the importance of NK cells in xenograft rejection, we studied EC activation and cytotoxicity in co-cultures containing human Mt cells and porcine EC, The addition of freshly isolated Mt cells to porcine EC resulted in EC cell activation, characterized by the induction of mRNA and protein for the adhesion molecule E-selectin and the chemotactic cytokine interleukin (IL)-8. The induction of E-selectin and IL-8 occurred with three separate sources of NK cells: purified CD56+ve cells, the NK cell clone B22, and the Fc receptor-deficient NK cell line NK92. Tran-swell cultures demonstrated that direct NK-EC contact was required for the EC induction of E-selectin and IL-8, These effects could not be inhibited with human recombinant tumor necrosis factor-alpha receptor, and the transfer of supernatants or cell lysates from activated EC to secondary cultures did not result in EC activation, The addition of human IgG enhanced the level of E-selectin expression and cellular cytotoxicity, and resulted in tumor necrosis factor-alpha and interferon-gamma secretion, Thus, human Mt cells can lyse or activate EC by direct cell contact and the addition of IgG enhances EC activation and NK cell cytokine secretion, These findings implicate NK cells in EC activation and cell-mediated xenograft rejection.