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小鼠异种移植中的移植物排斥反应:利用巨噬细胞归巢特性的体内磁共振成像诊断

Graft rejection in the xenogeneic transplantation of mice: diagnosis with in vivo MR imaging using the homing trait of macrophages.

作者信息

Mun Han Song, Kang Hee Jung, Lim Keun Ho, Sohn Jin Young, Chang Hyeujin, Lee Kyoung Geun, Lee Jin Seong

机构信息

Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Korea.

出版信息

Xenotransplantation. 2008 Jul-Aug;15(4):218-24. doi: 10.1111/j.1399-3089.2008.00479.x.

DOI:10.1111/j.1399-3089.2008.00479.x
PMID:18957044
Abstract

BACKGROUND

To evaluate the feasibility of magnetic resonance (MR) imaging to depict the in vivo recruitment of superparamagnetic iron oxide (SPIO)-labeled macrophages and to diagnose graft rejection in xenogeneic transplantation.

METHODS

We transplanted the trachea of SD rat (xenogeneic) or C3H/HeN mouse (syngeneic) into the left thighs of six male C3H/HeN mice. The SPIO-labeled macrophage was administered through the tail vein 2 days (acute) or 14 days (chronic) after transplantation in each group. The left thighs of the mice were imaged on a 4.7-T MR scanner 24 h after macrophage administration. We evaluated the extent and pattern of the susceptibility effect (macrophage distribution) and compared them in the two groups. The MR findings were then correlated with the histopathologic results. We also measured in both groups the monocyte chemoattractant protein (MCP)-1 level before and 2 days, 2 weeks, and 4 weeks after transplantation.

RESULTS

The band-shaped lower signal intensity (SI) zone was noted around the graft in the acute and chronic phases of xenogeneic group and in the acute phase of syngeneic group, but it was not noted in the chronic phase of syngeneic transplantation. The lower SI zone corresponded to the distribution of SPIO-labeled macrophages on histopathological analyses. On histologic examination, the severe inflammation developed around the xenogeneic graft, but only slightly around the syngeneic graft. MCP-1 was elevated 2 days after transplantation in both groups, but then gradually decreased in the syngeneic group; in xenogenic group, the MCP-1 value decreased by week 2 but then increased by week 4.

CONCLUSIONS

This study demonstrates that the homing of intravenously administered SPIO-labeled macrophages can be monitored on MR imaging and is correlated with the MCP-1 level and the histopathologic findings of the xenograft rejection.

摘要

背景

评估磁共振(MR)成像描绘超顺磁性氧化铁(SPIO)标记巨噬细胞的体内募集情况以及诊断异种移植中移植物排斥反应的可行性。

方法

我们将SD大鼠(异种)或C3H/HeN小鼠(同基因)的气管移植到6只雄性C3H/HeN小鼠的左大腿。每组在移植后2天(急性)或14天(慢性)通过尾静脉给予SPIO标记的巨噬细胞。巨噬细胞给药后24小时,在4.7-T MR扫描仪上对小鼠的左大腿进行成像。我们评估了磁化率效应(巨噬细胞分布)的范围和模式,并在两组之间进行比较。然后将MR结果与组织病理学结果相关联。我们还测量了两组在移植前以及移植后2天、2周和4周时的单核细胞趋化蛋白(MCP)-1水平。

结果

在异种移植组的急性和慢性期以及同基因移植组的急性期,移植物周围可见带状低信号强度(SI)区,但在同基因移植的慢性期未观察到。组织病理学分析显示,低SI区对应于SPIO标记巨噬细胞的分布。组织学检查发现,异种移植物周围出现严重炎症,而同基因移植物周围仅有轻微炎症。两组在移植后2天MCP-1均升高,但同基因移植组随后逐渐下降;异种移植组MCP-1值在第2周下降,但在第4周又升高。

结论

本研究表明,静脉注射SPIO标记巨噬细胞的归巢情况可通过MR成像监测,且与MCP-1水平及异种移植物排斥反应的组织病理学结果相关。

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