The Multiple Chemokine-Binding Bovine Herpesvirus 1 Glycoprotein G (BHV1gG) Inhibits Polymorphonuclear Cell but Not Monocyte Migration into Inflammatory Sites
The Multiple Chemokine-Binding Bovine Herpesvirus 1 Glycoprotein G (BHV1gG) Inhibits Polymorphonuclear Cell but Not Monocyte Migration into Inflammatory Sites
复制标题
多种趋化因子结合牛疱疹病毒 1 糖蛋白 G (BHV1gG) 抑制多形核细胞而非单核细胞迁移至炎症部位
DOI：
10.2119/molmed.2012.00339
复制
发表时间：
2013
影响因子：
5.7
通讯作者：
A. Davidson
中科院分区：
文献类型：
--
作者：
Zheng Liu;R. Bethunaickan;R. Sahu;M. Brenner;T. Laragione;P. Gulko;A. Davidson
趋化因子促进炎症细胞在组织中的募集，在广泛的炎症性和自身免疫性疾病中促进靶器官损伤。在类风湿性关节炎和狼疮的动物模型中，靶向单一趋化因子或趋化因子受体都可以改变疾病的进展，效果各不相同，但在人类身上的临床试验一直不太成功。鉴于趋化因子-趋化因子受体相互作用的冗余性，可能需要靶向一种以上的趋化因子来抑制活动性炎症性疾病。为了测试多种趋化因子阻断在炎症中的作用，我们制备了一种表达牛疱疹病毒1型糖蛋白G(BHV1gG)的腺病毒，它是一种病毒趋化因子拮抗剂，可与多种鼠和人趋化因子结合，并与小鼠免疫球蛋白(Ig G)2a的片段结晶(Fc)部分融合。腺病毒的应用显著抑制了硫代乙醇酸诱导的中性粒细胞向BALB/c小鼠腹膜腔内的迁移，并减轻了K/BxN血清转移诱导的关节炎的临床严重程度和关节损害。然而，在硫代乙酸酯模型中，BHV1gG-Ig融合蛋白的治疗不能阻止单核细胞向腹膜的渗透，也不能防止狼疮易感的NZB/W小鼠的肾脏单核细胞渗透或肾炎。这些观察结果表明，BHV1gG同时抑制多种趋化因子有可能干扰多形核白细胞介导的急性炎症反应，但对巨噬细胞介导的慢性炎症性疾病效果较差。
Chemokines facilitate the recruitment of inflammatory cells into tissues, contributing to target organ injury in a wide range of inflammatory and autoimmune diseases. Targeting either single chemokines or chemokine receptors alters the progression of disease in animal models of rheumatoid arthritis and lupus with varying degrees of efficacy, but clinical trials in humans have been less successful. Given the redundancy of chemokine-chemokine receptor interactions, targeting of more than one chemokine may be required to inhibit active inflammatory disease. To test the effects of multiple chemokine blockade in inflammation, we generated an adenovirus expressing bovine herpesvirus 1 glycoprotein G (BHV1gG), a viral chemokine antagonist that binds to a wide spectrum of murine and human chemokines, fused to the fragment crystallizable (Fc) portion of murine immunoglobulin (IgG)2a. Administration of the adenovirus significantly inhibited thioglycollate-induced migration of polymorphonuclear leukocytes into the peritoneal cavity of BALB/c mice and reduced both clinical severity and articular damage in K/BxN serum transfer-induced arthritis. However, treatment with BHV1gG-Ig fusion protein did not prevent monocyte infiltration into the peritoneum in the thioglycollate model and did not prevent renal monocyte infiltration or nephritis in lupus-prone NZB/W mice. These observations suggest that the simultaneous inhibition of multiple chemokines by BHV1gG has the potential to interfere with acute inflammatory responses mediated by polymorphonuclear leukocytes, but is less effective in chronic inflammatory disease mediated by macrophages.
登录
查看更多内容
影响因子：
--
作者：
Jacobs, Jonathan P.;Ortiz-Lopez, Adriana;Campbell, James J.;Gerard, Craig J.;Mathis, Diane;Benoist, Christophe
通讯作者：
Benoist, Christophe
影响因子：
--
作者：
B. Zheng;Zeynep Ozen;Xuejun Zhang;S. De Silva;E. Marinova;Linjie Guo;Daniel L. Wansley;D. Huston;M. West;Shuhua Han
通讯作者：
B. Zheng;Zeynep Ozen;Xuejun Zhang;S. De Silva;E. Marinova;Linjie Guo;Daniel L. Wansley;D. Huston;M. West;Shuhua Han
影响因子：
--
作者：
Liu, Zheng;Bethunaickan, Ramalingam;Huang, Weiqing;Lodhi, Umairullah;Solano, Ingrid;Madaio, Michael P.;Davidson, Anne
通讯作者：
Davidson, Anne
影响因子：
--
作者：
Laragione, Teresina;Brenner, Max;Sherry, Barbara;Gulko, Percio S.
通讯作者：
Gulko, Percio S.