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Allograft Rejection by Nature Immunity which Consist of Allograft Induced Macrophages

由同种异体移植诱导的巨噬细胞组成的自然免疫引起的同种异体移植排斥

基本信息

批准号：
20791129
负责人：
NOMI Hayahito
金额：
$ 2.58万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

项目摘要

At first, we analyzed in tumor cells of allogeneic transplantation models, because it turned out to require more time beyond our expectation to achieve the clear result of suppressing macrophages from allogeneic organ transplantation mouse models. We have already reported that 3 × 10^6 cells Meth A fibro-sarcoma (MA cells) which were allo-transplantated into peritoneal space of a C57BL/6 mouse completely rejected in about 14 days. We have also reported that allograft-induced macrophages (AIM) were effective mainly as cellular disorder of peritoneal infiltrating which were activated in this rejection. MA cells have been known to be CTL resistant cells. In this study, we used GFP transgenic C57BL/6 mice (GFP-mice) for the donors and we finally succeeded in videotaping that the GFP-AIM were biting off the co-cultured allogeneic MA cells. We were sure that the bited off allo-MA cells from this achievement. But, we now have to solve the critical problems whether biting off abilities of the AIM are exert toward allogeneic or neoplastic changes of MA. Now we are examining the ability of AIM derived from PEC to solve this problem, after removing some AIM cells which can respond to neoplastic changes. In addition, we are investigating time course of fluorescence shift of the cells PEC drive adherent cells mainly consist from GFP-AIM with or without various concentration of some of agents influence to macrophage, like as Tranilast(3μM~300μM). We, however, have not found out critical effect of it yet. Next, we will try it in activation phase of AIM.

首先，我们分析了异基因移植模型的肿瘤细胞，因为事实证明需要比我们预期更多的时间来实现抑制异基因器官移植小鼠模型巨噬细胞的明确结果。我们已经报道了将3 × 10^6个细胞的MethA纤维肉瘤（MA细胞）同种异体移植到C57 BL/6小鼠的腹腔内，在大约14天内完全排斥。我们还报道了同种异体移植物诱导的巨噬细胞（AIM）主要作为在这种排斥反应中被激活的腹膜浸润的细胞紊乱而有效。已知MA细胞是CTL抗性细胞。在这项研究中，我们使用GFP转基因C57 BL/6小鼠（GFP小鼠）作为供体，我们最终成功地拍摄了GFP-AIM咬下共培养的同种异体MA细胞的视频。我们确信，从这一成就中咬下的allo-MA细胞。但是，AIM的咬噬能力是否对MA的同种异体或肿瘤性改变发挥作用，是目前需要解决的关键问题。现在，我们正在研究从PEC中提取的AIM在去除一些能够对肿瘤变化做出反应的AIM细胞后解决这个问题的能力。此外，我们还研究了在不同浓度的曲尼司特（3μM~300μM）等对巨噬细胞有影响的药物的存在下，以GFP-AIM为主要成分的PEC驱动的贴壁细胞荧光位移的时间过程。然而，我们还没有发现它的关键作用。接下来，我们将在AIM的激活阶段尝试它。