Blockade of VEGF receptor-3 aggravates inflammatory bowel disease and lymphatic vessel enlargement.
Blockade of VEGF receptor-3 aggravates inflammatory bowel disease and lymphatic vessel enlargement.
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DOI：
10.1097/mib.0b013e31829292f7
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发表时间：
2013-08
影响因子：
4.9
通讯作者：
Detmar M
中科院分区：
文献类型：
--
作者：
Jurisic G;Sundberg JP;Detmar M
与血管系统在促进组织炎症中的突出功能相反，淋巴血管在炎症中的作用在体内的研究很少。为了研究调节淋巴管功能是否会影响慢性炎症的进程，在一个已建立的炎症性肠病模型中，主要淋巴管生成受体血管生长因子受体3 （VEGFR-3, FLT4）被阻断。用VEGFR-3阻断抗体治疗自发发生炎症性肠病的白细胞介素10 （IL10）缺陷小鼠2周，定量分析结肠组织的炎症变化以及血液和淋巴血管化。我们发现抗vegfr -3治疗小鼠的结肠炎症严重程度显著增加。伴有淋巴管增大和弯曲的数量增加，结肠粘膜下层水肿，表明淋巴功能受损。相比之下，没有观察到治疗对血管系统的主要影响。这些结果表明，旨在促进淋巴功能的疗法，例如使用促淋巴管生成因子（如VEGF-C），可能为治疗炎症性肠病等炎症性疾病提供一种新的策略。
In contrast to the prominent function of the blood vasculature in promoting tissue inflammation, the role of lymphatic vessels in inflammation has been scarcely studied in vivo. To investigate whether modulating lymphatic vessel function might affect the course of chronic inflammation the major lymphangiogenic receptor vascular growth factor receptor 3 (VEGFR-3, FLT4) was blocked in an established model of inflammatory bowel disease. Interleukin 10 (IL10)-deficient mice that spontaneously develop inflammatory bowel disease, were treated with a blocking antibody to VEGFR-3 for 2 weeks, and the inflammatory changes in colon tissue, as well as the blood and lymphatic vascularization were quantitatively analyzed. We found a significant increase in the severity of colon inflammation in anti-VEGFR-3 treated mice. This was accompanied by an increased number of enlarged and tortuous lymphatic vessels, and edema in colon submucosa, indicating impaired lymphatic function. In contrast, no major effects of the treatment on the blood vasculature were observed. These results indicate that therapies aimed at promoting lymphatic function, e.g., with pro-lymphangiogenic factors such as VEGF-C, might provide a novel strategy for the treatment of inflammatory conditions such as inflammatory bowel disease.