Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants
Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants
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DOI：
10.1038/nm1340
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发表时间：
2006-02-01
期刊：
影响因子：
82.9
通讯作者：
Mazal, PR
中科院分区：
文献类型：
--
作者：
Kerjaschki, D;Huttary, N;Mazal, PR
从头淋巴管生成影响不同人类疾病的进程，包括慢性肾移植排斥(1) 和肿瘤转移(2,3)。人类疾病中淋巴管生成的细胞机制目前尚不清楚，可能涉及局部预先存在的内皮细胞的分裂或循环祖细胞的掺入。我们分析了接受性别不匹配移植的个体的肾组织，这些个体存在移植排斥、总体淋巴内皮增殖率高以及大量慢性炎症。通过 Y 染色体原位杂交检测供体来源的细胞。我们将这些组织与基本正常的皮肤和肠道的活检组织以及两种淋巴管内皮增殖率低的罕见癌症进行了比较，这些癌症来自性别不匹配的骨髓移植个体。在这里，我们提供了受体来源的淋巴祖细胞参与肾移植的证据。相比之下，正常组织和移植后癌周围的淋巴管不包含供体来源的祖细胞。这表明炎症相关的从头淋巴管生成的逐步机制，意味着潜在的淋巴祖细胞来自循环，通过结缔组织基质迁移，可能以巨噬细胞的形式，最后并入生长的淋巴管。
De novo lymphangiogenesis influences the course of different human diseases as diverse as chronic renal transplant rejection(1) and tumor metastasis(2,3). The cellular mechanisms of lymphangiogenesis in human diseases are currently unknown, and could involve division of local preexisting endothelial cells or incorporation of circulating progenitors. We analyzed renal tissues of individuals with gender-mismatched transplants who had transplant rejection and high rates of overall lymphatic endothelial proliferation as well as massive chronic inflammation. Donor-derived cells were detected by in situ hybridization of the Y chromosome. We compared these tissues with biopsies of essentially normal skin and intestine, and two rare carcinomas with low rates of lymphatic endothelial proliferation that were derived from individuals with gender-mismatched bone marrow transplants. Here, we provide evidence for the participation of recipient-derived lymphatic progenitor cells in renal transplants. In contrast, lymphatic vessels of normal tissues and those around post-transplant carcinomas did not incorporate donor-derived progenitors. This indicates a stepwise mechanism of inflammation-associated de novo lymphangiogenesis, implying that potential lymphatic progenitor cells derive from the circulation, transmigrate through the connective tissue stroma, presumably in the form of macrophages, and finally incorporate into the growing lymphatic vessel.