Angiogenesis in the huPBL-SCID model of human transplant rejection

Angiogenesis in the huPBL-SCID model of human transplant rejection
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DOI:
10.1097/00007890-199906270-00020
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发表时间:
1999-06-27
期刊:
影响因子:
6.2
通讯作者:
Briscoe, DM
Briscoe, DM
中科院分区:
医学2区
文献类型:
--
作者:
Moulton, KS;Melder, RJ;Briscoe, DM

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背景。血管生成是慢性炎症反应的特征。据报道,血管生成过程是促炎的,部分是由于粘附事件增强,部分是由于炎症部位的灌注和渗透性增加。 However, little is known about the association between angiogenesis and rejection.Methods.严重联合免疫缺陷小鼠允许人皮肤同种异体移植物和人外周血单核细胞(PBMC)的生长。通过静脉内或腹膜内注射将人PBMC注射到小鼠体内。通过视频显微镜对皮肤同种异体移植物中的细胞浸润和相关血管生成反应进行时间分析,并通过免疫组织化学进行空间分析。结果。静脉输注 PBMC 后数小时内,人类同种异体反应性单核细胞迁移到人类皮肤,但没有迁移到小鼠皮肤。 3天内,在浸润部位的皮肤移植物中观察到血管生成区域。输注当天基线时,皮肤移植物的血管密度为每个校准网格 24+/-6 根血管,到第 10 天增加到每个校准区域 55+/-16 根血管。腹膜内输注人 PBMC 7-14 天后,从人源化严重联合免疫缺陷小鼠收获的皮肤移植物显示出类似的血管密度增加,与单核细胞浸润在空间上相关。结论。显着的血管生成反应与人皮肤同种异体移植物中的细胞浸润相关。 UF血管生成的开始出现在局部浸润的最初发展之后并且在微血管破坏的发展之前。这些发现表明同种异体反应性 T 细胞和/或单核细胞介导皮肤同种异体移植物中的血管生成反应。
Background. Angiogenesis is characteristic of chronic inflammatory reactions. The process of angiogenesis is reported to be proinflammatory in part due to enhanced adhesion events and in part due to increased perfusion and permeability to sites of inflammation. However, little is known about the association between angiogenesis and rejection.Methods. Severe combined immune deficient mice are permissive for the growth of human skin allografts and human peripheral blood mononuclear cells (PBMC). Human PBMC were injected into mice by intravenous or intraperitoneal injection. The infiltration of cells and the associated angiogenesis reactions in the skin allografts were analyzed temporally by videomicroscopy and spatially by immunohistochemistry.Results. Human alloreactive mononuclear cells migrated to human skin but not mouse skin within hours after the intravenous infusion of PBMC. Within 3 days, areas of angiogenesis were observed in the skin grafts at the sites of infiltrates. The vessel densities in skin grafts were 24+/-6 vessels per calibrated grid at baseline on the day of the infusion and increased to 55+/-16 vessels per calibrated field by day 10. Skin grafts harvested from humanized severe combined immune deficient mice 7-14 days after the intraperitoneal infusion of human PBMC showed a similar increased density of vessels that were spatially associated with mononuclear cell infiltrates.Conclusions. A significant angiogenesis response was associated with the cell infiltrates in the human skin allografts. The onset uf angiogenesis appeared after the initial development of localized infiltrates and preceded the development of microvascular destruction. These findings suggest that alloreactive T cells and/or monocytes mediate the angiogenesis response in skin allografts.