Full Text:   <912>

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CLC number: S852.35; R363.2

On-line Access: 2017-01-03

Received: 2016-11-03

Revision Accepted: 2016-11-28

Crosschecked: 2016-12-13

Cited: 0

Clicked: 2056

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Xun Tan

http://orcid.org/0000-0002-0897-9052

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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.1 P.59-69

http://doi.org/10.1631/jzus.B1600500


Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response


Author(s):  Xun Tan, Fan-guo Juan, Ali Q. Shah

Affiliation(s):  Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China

Corresponding email(s):   tanxun@zju.edu.cn

Key Words:  Plexiform lesions, Endothelial progenitor cells, Immune response, Hepatocyte growth factor, Broiler chicken


Xun Tan, Fan-guo Juan, Ali Q. Shah. Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response[J]. Journal of Zhejiang University Science B, 2017, 18(1): 59-69.

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%T Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response
%A Xun Tan
%A Fan-guo Juan
%A Ali Q. Shah
%J Journal of Zhejiang University SCIENCE B
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T1 - Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response
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EP - 69
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1600500


Abstract: 
plexiform lesions (PLs), which are often accompanied by perivascular infiltrates of mononuclear cells, represent the hallmark lesions of pulmonary arteries in humans suffering from severe pulmonary arterial hypertension (PAH). endothelial progenitor cells (EPCs) have been recently implicated in the formation of PLs in human patients. PLs rarely develop in rodent animal models of PAH but can develop spontaneously in broiler chickens. The aim of the present study was to confirm the presence of EPCs in the PLs in broilers. The immune mechanisms involved in EPC dysfunction were also evaluated. Lungs were collected from commercial broilers at 1 to 4 weeks of age. The right/total ventricle ratios indicated normal pulmonary arterial pressures for all sampled birds. Immunohistochemistry was performed to determine the expressions of EPC markers (CD133 and VEGFR-2) and proangiogenic molecule hepatocyte growth factor (HGF) in the lung samples. An EPC/lymphocyte co-culture system was used to investigate the functional changes of EPCs under the challenge of immune cells. PLs with different cellular composition were detected in the lungs of broilers regardless of age, and they were commonly surrounded by moderate to dense perivascular mononuclear cell infiltrates. Immunohistochemical analyses revealed the presence of CD133+ and VEGFR-2+ cells in PLs. These structures also exhibited a strong expression of HGF. Lymphocyte co-culture enhanced EPC apoptosis and completely blocked HGF-stimulated EPC survival and in vitro tube formation. Taken together, this work provides evidence for the involvement of EPCs in the development of PLs in broilers. It is suggested that the local immune cell infiltrate might serve as a contributor to EPC dysfunction by inducing EPC death and limiting their response to angiogenic stimuli. broiler chickens may be valuable for investigating reversibility of plexogenic arteriopathy using gene-modified inflammation-resistant EPCs.

免疫炎症反应和内皮祖细胞在肉鸡肺血管丛样病变形成中的作用

目的:肺血管丛样病变是重度肺动脉高压(PAH)病人的特征病变,病变血管周围常伴有单个核细胞浸润。肺血管丛样病变在常用实验动物上难以复制,但可在肉鸡(一种生长快速的肉用型鸡)肺脏中自发形成。内皮祖细胞(EPCs)在组织再生和血管修复过程中发挥重要作用。本研究以肉鸡为模型,探讨EPCs与肺血管丛样病变形成之间的关系。
创新点:证实EPCs参与了肺血管丛样病变的形成过程,并揭示了导致EPCs功能障碍的免疫学机制。
方法:采集1~4周龄肉鸡肺组织,常规石蜡切片,观察肺血管丛样病变的形成情况;采用免疫组化法检测EPCs表面标志CD133和VEGFR-2的表达以及肝细胞生长因子(HGF)的表达;分离培养晚期EPCs,建立EPCs/淋巴细胞共培养体系,并在共培养体系中添加20 ng/ml HGF,观察EPCs增殖、凋亡和体外管样结构形成的变化。
结论:在不同周龄的肉鸡肺组织中均可观察到处于不同发展阶段的肺血管丛样病变(图1)。早期的丛样病变主要由EPCs(CD133+和VEGFR-2+细胞)构成,HGF在病变实体中高表达(图2)。淋巴细胞共培养显著促进EPCs凋亡(图5),并能阻断HGF诱导的EPCs存活和体外管样结构形成(图6)。综上所述,肺血管丛样病变的形成可能与局部免疫炎症反应诱导EPCs凋亡并下调EPCs对促血管生成因子的反应性有关。

关键词:丛样病变;内皮祖细胞;免疫反应;肝细胞生长因子;肉鸡

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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