The immunogenicity of the extracellular matrix in arterial xenografts
The immunogenicity of the extracellular matrix in arterial xenografts
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DOI：
10.1016/s0039-6060(97)90267-1
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发表时间：
1997-07-01
期刊：
影响因子：
3.8
通讯作者：
Michel, JB
中科院分区：
文献类型：
--
作者：
Allaire, E;Bruneval, P;Michel, JB
背景资料。异种移植免疫原性的决定因素还没有得到很好的描述。先前的研究表明，脱细胞异种动脉(DAX)扩张，而脱细胞同种异体动脉(DAL)和同种异体移植物不扩张，提示动脉细胞外基质的种间免疫原性而不是种内免疫原性导致慢性排斥。现在我们研究了异种移植物中动脉细胞外基质的免疫原性及其对慢性损伤(弹性蛋白溶解)和重塑(移植物扩张)的影响。8周龄时测量金黄地鼠DAL和DAX的直径和弹性蛋白含量，并在植入后6h~4周用免疫组织化学方法检测DAL和DAX的免疫效应。将结果与未脱细胞同种异体移植物和异种移植物进行比较。最后，在三种异种移植组合中评估供受者系统发育距离对单核细胞-巨噬细胞穿透能力的影响。结果豚鼠的DAX在8周时形成动脉瘤，而不是来自仓鼠的DAX。弹性蛋白溶解与移植物扩张平行。DAX被单核细胞、巨噬细胞、T淋巴细胞和免疫球蛋白渗透，而不是DAL。供受者组合并不影响DAX中炎性浸润物的表型，但它改变了单核-巨噬细胞穿透介质的动力学。脱细胞改变了炎性浸润表型(巨噬细胞缺失)，但对DAX的损伤和重建影响不大。结论DAX的免疫原性是受供受者组合调控的慢性异种动脉移植损伤的主要原因。动脉异种移植物的免疫原性与同种异体移植物不同，除了细胞外，还受到细胞外基质的支持，并可能影响异种移植物的长期命运。
Background. Determinants of xenograft immunogenicity are poorly characterized. The showed previously that decellularized arterial xenografts (DAXs) dilate, whereas decellularized arterial isografts (DAls) and allografts do not, suggesting an interspecies, rather than an intraspecies, immunogenicity of the arterial extracellular matrix leading to chronic rejection. Now we have investigated the immunogenicity of the arterial extracellular matrix in xenografts and its impact on chronic injury (elastin lysis) and remodeling (graft dilation).Methods. Diameter and elastin content were measured in DAls and DAXs from hamster do mt (concordant combination) and guinea pig to rat (discordant combinations) at 8 weeks, We also characterized the immune effecters infiltrating DAls and DAXs by immunohistochemistry after 6 hours to 4 weeks of implantation. Results were compared with nondecellularized isografts and xenografts. Last, the impact of the donor-recipient phylogenetic distance on monocyte-macrophage penetration into the media was assessed in three xenograft combinations.Results, DAXs from guinea pig, but not from hamster, were aneurysmal at 8 weeks. Elastin lysis paralleled graft dilation. DAXs, but not DAls, were infiltrated by monocytes, macrophages, T lymphocytes, and immunoglobulins. The donor-recipient combination did not effect the phenotype of the inflammatory infiltrate in DAXs, but it modified the kinetics of monocyte-macrophage penetration into the media. The absence of decellularization changed the inflammatory infiltrate phenotype (absence of macrophages) but had little impact on DAX injury and remodeling.Conclusions, DAX immunogenicity accounts for most of chronic arterial xenograft injury which is modulated by the donor-recipient combination. The immunogenicity of arterial xenografts, unlike allografts, is supported by the extracellular matrix in addition to the cells and could influence the long-term fate of xenografts.