汉坦病毒感染对β3整合素及血管内皮生长因子受体2的作用

The impact of hantavirus infection on β3 integrins and VEGFR2

目的探讨汉坦病毒(HV)感染后β3整合素与血管内皮生长因子受体2(VEGFR2)的变化及其对内皮功能的影响。方法本研究以体外培养的人脐静脉内皮细胞(HUVEC)为对象,应用黏附试验、Transwell技术及流式细胞技术,观察HV感染后HUVEC黏附和迁移能力的变化,分析β3整合素与VEGFR2在其中的作用及二者表达数量的变化。结果 HV明显抑制HUVEC黏附和迁移能力(P<0.05)。VEGF促进内皮细胞的黏附和迁移的能力可被β3整合素拮抗剂或HV感染所阻断(P<0.05),VEGF促进β3整合素表达的作用也可被HV抑制(P<0.05)。HV可以促进β3整合素及VEGFR2的表达(P<0.05),且二者呈密切正相关(r=0.846)。结论 HV感染对β3整合素、VEGFR2的功能及表达数量的影响可能是其致病机制之一。

Objective Hantaviruses infect human vascular endothelial cells and cause two vascular permeability-based highly lethal diseases：hemorrhagic fever with renal syndrome（HFRS）and hantavirus pulmonary syndrome（HPS）.Hemorrhagic diseases and vascular permeability deficits are consequences of dysfunctional β3 integrins that normally regulate vascular endothelial growth factor（VEGF） responses.β3 integrins and vascular permeability factor receptor-2（VEGFR-2） affect each other,and form functional complex.β3 integrins are important receptors used by hantaviruses for cell attachment and entry.The objective of this study is to explore the impact of hantavirus infection on β3 integrins and vascular VEGFR-2.Methods The strain of HV 76-118 was applied to infect human umbilical vein endothelial cell（HUVEC） lines（vero-E6）.The adhesion and migration effects of hantavirus infection in HUVEC were observed by the assays of adhesion test,membrane transwell technique and flow cytometry.The changes of β3 integrins and VEGFR2 expression levels were evaluated for hantavirus infection.Results The infection of hantavirus significantly inhibited the abilities of migration and adhesion of HUVEC（P〈0.05）.The vascular permeability of VEGF could be decreased dramatically by anti-β3 integrins or hantavirus infection（P〈0.05）.The expression of VEGFR2 was improved with hantanvirus infection,which might be associated with over expression of β3 integrins.Conclusions The pathogenesis of hyper permeability with hantavirus infection is caused by the dysfunction of VEGFR2 and β3 integrins complex.