Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis

详细信息    查看全文

• 作者：Robin Kahn¹ ; Maria Mossberg¹ ; Anne-lie Stå ; hl¹ ; Karl Johansson¹ ; Ingrid Lopatko Lindman¹ ; Caroline Heijl² ; Må ; rten Segelmark³ ; Matthias M&ouml ; rgelin⁴ ; L.M. Fredrik Leeb-Lundberg⁵ ; Diana Karpman¹ ; ^{diana.karpman@med.lu.se}
• 关键词：ANCA ; bradykinin ; kinin receptors ; microvesicles ; vasculitis
• 刊名：Kidney International
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：91
• 期：1
• 页码：96-105
• 全文大小：2288 K
• 卷排序：91

文摘

During vasculitis, activation of the kinin system induces inflammation, whereby the kinin B1-receptor is expressed and activated after ligand binding. Additionally, activated blood cells release microvesicles into the circulation. Here we determined whether leukocyte-derived microvesicles bear B1-kinin receptors during vasculitis, and if microvesicles transfer functional B1-receptors to recipient cells, thus promoting inflammation. By flow cytometry, plasma from patients with vasculitis were found to contain high levels of leukocyte-derived microvesicles bearing B1-receptors. Importantly, renal biopsies from two patients with vasculitis showed leukocyte-derived microvesicles bearing B1-receptors docking on glomerular endothelial cells providing in vivo relevance. Microvesicles derived from B1-receptor-transfected human embryonic kidney cells transferred B1-receptors to wild-type human embryonic kidney cells, lacking the receptor, and to glomerular endothelial cells. The transferred B1-receptors induced calcium influx after B1-receptor agonist stimulation: a response abrogated by a specific B1-receptor antagonist. Microvesicles derived from neutrophils also transferred B1-receptors to wild-type human embryonic kidney cells and induced calcium influx after stimulation. Thus, we found a novel mechanism by which microvesicles transfer functional receptors and promote kinin-associated inflammation.