Lymphatic vascularisation and involvement of Lyve-1+ macrophages in the human onchocerca nodule.

Lymphatic vascularisation and involvement of Lyve-1+ macrophages in the human onchocerca nodule.
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DOI:
10.1371/journal.pone.0008234
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发表时间:
2009-12-09
期刊:
影响因子:
3.7
通讯作者:
Martin C
Martin C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Attout T;Hoerauf A;Dénécé G;Debrah AY;Marfo-Debrekyei Y;Boussinesq M;Wanji S;Martinez V;Mand S;Adjei O;Bain O;Specht S;Martin C

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盘尾丝虫病由丝虫性线虫盘尾丝虫引起,是一种寄生虫病,可导致衰弱性皮肤病和失明,并造成重大的经济和社会后果。盘尾丝虫病的病理学主要被认为是长期存在的宿主炎症反应的结果。在盘尾丝虫病中,在雌蠕虫周围形成皮下结节,其核心是炎性细胞的密集浸润,其中释放微丝蚴。已经确定结节的形成与血管生成有关。在这项研究中,我们使用内皮细胞(CD 31)和淋巴管内皮细胞(Lyve-1,Podoplanin)的特异性标志物表明,结节内不仅发生血管生成,而且发生淋巴管生成。7%的微丝蚴位于结节内的血管内,但在结节内的血管内均未发现微丝蚴,提示微丝蚴可能有一条迁移途径。新血管形成与盘尾丝虫病患者结节中血管/淋巴管生成因子的特定模式相关,其特征在于CXCL 12、CXCR 4、VEGF-C、血管生成素-1和血管生成素-2的表达。有趣的是,发现一部分巨噬细胞对Lyve-1呈阳性,一些巨噬细胞整合到淋巴管的内皮中,揭示了它们在结节微环境中的可塑性。这些结果表明,淋巴管以及周围的血液血管化诱导O。肠扭转蠕虫,或者通过寄生虫本身,例如通过血管生成和淋巴管生成因子的释放,或者通过连续的宿主免疫应答。
Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is a parasitic disease leading to debilitating skin disease and blindness, with major economic and social consequences. The pathology of onchocerciasis is principally considered to be a consequence of long-standing host inflammatory responses. In onchocerciasis a subcutaneous nodule is formed around the female worms, the core of which is a dense infiltrate of inflammatory cells in which microfilariae are released. It has been established that the formation of nodules is associated with angiogenesis. In this study, we show using specific markers of endothelium (CD31) and lymphatic endothelial cells (Lyve-1, Podoplanin) that not only angiogenesis but also lymphangiogenesis occurs within the nodule. 7% of the microfilariae could be found within the lymphatics, but none within blood vessels in these nodules, suggesting a possible route of migration for the larvae. The neovascularisation was associated with a particular pattern of angio/lymphangiogenic factors in nodules of onchocerciasis patients, characterized by the expression of CXCL12, CXCR4, VEGF-C, Angiopoietin-1 and Angiopoietin-2. Interestingly, a proportion of macrophages were found to be positive for Lyve-1 and some were integrated into the endothelium of the lymphatic vessels, revealing their plasticity in the nodular micro-environment. These results indicate that lymphatic as well as blood vascularization is induced around O. volvulus worms, either by the parasite itself, e.g. by the release of angiogenic and lymphangiogenic factors, or by consecutive host immune responses.
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发表时间: 2006-09-01
期刊: PLOS PATHOGENS
影响因子: 6.7
作者:
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通讯作者: Hoerauf, Achim
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发表时间: 2003-06-01
影响因子: 1.5
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DOI: 10.1172/jci200420465
发表时间: 2004-04-01
影响因子: 15.9
作者:
Cursiefen, C;Chen, L;Streilein, JW
通讯作者: Streilein, JW