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

被引：45

作者：

Kahn, Robin ^{[1
]}

Mossberg, Maria ^{[1
]}

Stahl, Anne-lie ^{[1
]}

Johansson, Karl ^{[1
]}

Lindman, Ingrid Lopatko ^{[1
]}

Heijl, Caroline ^{[2
]}

Segelmark, Marten ^{[3
]}

Morgelin, Matthias ^{[4
]}

Leeb-Lundberg, L. M. Fredrik ^{[5
]}

Karpman, Diana ^{[1
]}

机构：

[1] Lund Univ, Clin Sci Lund, Dept Pediat, S-22185 Lund, Sweden

[2] Lund Univ, Clin Sci Lund, Dept Nephrol, Lund, Sweden

[3] Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden

[4] Lund Univ, Clin Sci Lund, Dept Infect Med, Lund, Sweden

[5] Lund Univ, Dept Expt Med Sci, Div Pharmacol & Struct Biol, Unit Drug Target Discovery, Lund, Sweden

来源：

KIDNEY INTERNATIONAL | 2017年 / 91卷 / 01期

基金：

瑞典研究理事会;

关键词：

ANCA; bradykinin; kinin receptors; microvesicles; vasculitis; CELL-DERIVED MICROPARTICLES; HEMOLYTIC-UREMIC SYNDROME; PLATELET MICROPARTICLES; RECEPTOR ENDOCYTOSIS; IMMUNE-RESPONSES; CONTACT-SYSTEM; B1; RECEPTORS; ACTIVATION; RELEASE; B-1;

D O I：

10.1016/j.kint.2016.09.023

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：96 / 105

页数：10

共 44 条

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