Lymphatic microvessels in the rat remnant kidney model of renal fibrosis: Aminopeptidase P and podoplanin are discriminatory markers for endothelial cells of blood and lymphatic vessels
Lymphatic microvessels in the rat remnant kidney model of renal fibrosis: Aminopeptidase P and podoplanin are discriminatory markers for endothelial cells of blood and lymphatic vessels
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DOI：
10.1097/01.asn.0000076078.50889.43
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发表时间：
2003-08-01
影响因子：
13.6
通讯作者：
Kerjaschki, D
中科院分区：
文献类型：
--
作者：
Matsui, K;Nagy-Bojarsky, K;Kerjaschki, D
大鼠残肾是一种已建立的肾小管间质纤维化和进展为终末期肾功能衰竭的模型。形态损害包括肾单位丢失和再生性肾小管肥大、以巨噬细胞为主的间质浸润和进行性纤维化。在这一复杂的病理过程中，肾小管间质微血管起着关键作用，它调节肾小管的氧气和营养物质的供应。虽然一些研究报告了与皮质退行性改变相关的血管网络稀疏，但另一些研究发现血管形成增加。在这里，这些差异的发现通过使用两个新的内皮细胞系特异的区分标记物来重新研究大鼠残肾的血管形成，即淋巴管内皮细胞特异性的膜粘蛋白PodoPlanin和糖基磷脂酰肌醇(GPI)锚定的膜酶氨基肽酶P，该酶可由一种名为JG12的单抗识别并且仅由血管内皮细胞特异性表达。这些结果证实了氨基肽酶P阳性微血管的局部稀疏；它们也证实了肾淋巴管系统的重大变化。肾小管间质纤维化区淋巴管大量增殖，而假手术组大鼠肾脏仅见少数淋巴管与动脉毗邻。淋巴管内常含有间质中也可见的单个核细胞，原位杂交显示血管内皮生长因子-C基因表达较多。总而言之，这些结果表明，残肾皮质中的微血管有很大一部分是淋巴源性的，不能用淋巴和血液内皮细胞都表达的常见内皮标志物，如CD34来区分。由于淋巴管内皮细胞分泌趋化因子吸引树突状细胞，淋巴管血管化的增加有可能加强对残肾的免疫监测。
Rat remnant kidney is an established model of renal tubulointerstitial fibrosis and progression to end-stage renal failure. The morphologic lesions comprise nephron loss and regeneratory tubular hypertrophy, interstitial infiltration, predominately by macrophages, and progressive fibrosis. A critical role in this complex pathology was assigned to tubulointerstitial blood microvessels that regulate the supply of oxygen and nutrients of tubuli. Whereas some investigations reported a rarefaction of the vascular network in association with the degenerative cortical changes, others observed an increase in vascularization. Here these discrepant findings are addressed by reinvestigation of the vascularization of rat remnant kidneys by the use of two novel endothelial lineage specific, discriminatory markers, i.e., the membrane mucoprotein podoplanin with specificity for lymphatic endothelia, and the glycosylphosphatidylinositol (GPI)-anchored membrane enzyme aminopeptidase P that is recognized by a monoclonal antibody designated JG12 and that is specifically expressed by endothelial cells of blood vessels only. The results obtained confirm a regional rarefaction of aminopeptidase P-positive blood microvessels; they also establish major changes in the renal lymphatic vasculature. Massive proliferation of lymphatic vessels was observed in fibrotic tubulointerstitial regions, whereas in kidneys of sham-operated rats, only a few lymphatic vessels were found adjoined with arteries. The lymphatic vessels frequently contained mononuclear cells that were also encountered in the interstitial spaces and expressed relative large amounts of vascular endothelial growth factor-C mRNA by in situ hybridization. Collectively, these results indicate that a large proportion of the microvessels encountered in the cortex of remnant kidneys are of lymphatic origin and cannot be discriminated by common endothelial markers, such as CD34, that are expressed by both lymphatic and blood endothelia cells. As lymphatic endothelial cells secrete chemokines that attract dendritic cells, it is possible that the increase in lymphatic vascularization could enhance the immunologic surveillance of remnant kidneys.