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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • Linköping University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • ANCA, bradykinin, kinin receptors, microvesicles, vasculitis
Original languageEnglish
Pages (from-to)96-105
Number of pages10
JournalKidney International
Volume91
Issue number1
Publication statusPublished - 2017 Jan 1
Publication categoryResearch
Peer-reviewedYes

Related research output

Maria Mossberg, 2017, Lund: Lund University, Faculty of Medicine. 82 p.

Research output: ThesisDoctoral Thesis (compilation)

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