The role of CX₃CL1/CX₃CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome.
The role of CX₃CL1/CX₃CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome.
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DOI：
10.1016/j.jhep.2012.05.014
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发表时间：
2012-10
影响因子：
25.7
通讯作者：
Fallon, Michael B.
中科院分区：
文献类型：
--
作者：
Zhang, Junlan;Yang, Wenli;Luo, Bao;Hu, Bingqian;Maheshwari, Akhil;Fallon, Michael B.
Hepatopulmonary syndrome (HPS), classically attributed to intrapulmonary vascular dilatation, occurs in 15-30% of cirrhotics and causes hypoxemia and increased mortality. In experimental HPS after common bile duct ligation (CBDL), monocytes adhere in the lung vasculature and produce vascular endothelial growth factor (VEGF)-A and angiogenesis ensues and contributes to abnormal gas exchange. However, the mechanisms for these events are unknown. The chemokine fractalkine (CX3CL1) can directly mediate monocyte adhesion and activate VEGF-A and angiogenesis via its receptor CX3CR1 on monocytes and endothelium during inflammatory angiogenesis. We explored whether pulmonary CX3CL1/CX3CR1 alterations occur after CBDL and influence pulmonary angiogenesis and HPS. Pulmonary CX3CL1/CX3CR1 expression and localization, CX3CL1 signaling pathway activation, monocyte accumulation, and the development of angiogenesis and HPS were assessed in 2 and 4wk CBDL animals. The effects of a neutralizing antibody to CX3CR1 (anti-CX3CR1 Ab) on HPS after CBDL were evaluated. Circulating CX3CL1 levels and lung expression of CX3CL1 and CX3CR1 in intravascular monocytes and microvascular endothelium increased in 2 and 4wk CBDL animals as HPS developed. These events were accompanied by pulmonary angiogenesis, monocyte accumulation, activation of CX3CL1 mediated signaling pathways (Akt, ERK) and increased VEGF-A expression and signaling. Anti-CX3CR1 Ab treatment reduced monocyte accumulation, decreased lung angiogenesis and improved HPS. These events were accompanied by inhibition of CX3CL1 signaling pathways and a reduction in VEGF-A expression and signaling. Circulating CX3CL1 levels and pulmonary CX3CL1/CX3CR1 expression and signaling increase after CBDL and contribute to pulmonary intravascular monocyte accumulation, angiogenesis and the development of experimental HPS.
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影响因子：
29.4
作者：
Fallon, MB;Abrams, GA;Ku, DD
通讯作者：
Ku, DD
DOI：
10.1152/ajpheart.00113.2006
发表时间：
2006-12-01
影响因子：
4.8
作者：
Lee, Seon-Jin;Namkoong, Seung;Kim, Young-Myeong
通讯作者：
Kim, Young-Myeong
影响因子：
4.8
作者：
Kroll, J;Waltenberger, J
通讯作者：
Waltenberger, J
影响因子：
1.9
作者：
Aller, MA;Nava, MR;Arias, J
通讯作者：
Arias, J
影响因子：
4.4
作者：
Ishida, Yuko;Gao, Ji-Liang;Murphy, Philip M.
通讯作者：
Murphy, Philip M.