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

Robin Kahn, Maria Mossberg, Anne-Lie Ståhl, Karl Johansson, Ingrid Lopatko Lindman, Caroline Heijl, Mårten Segelmark, Matthias Mörgelin, L M Fredrik Leeb-Lundberg, Diana Karpman

Journal: Kidney international 2017;91(1):96-105

PMID: 27914700

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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.

Address: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.; Department of Nephrology, Clinical Sciences Lund, Lund University, Lund, Sweden.; Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.; Department of Infection Medicine, Clinical Sciences Lund, Lund University, Lund, Sweden.; Unit of Drug Target Discovery, Division of Pharmacology and Structural Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden.; Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address: [email protected].

DOI: 10.1016/j.kint.2016.09.023

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https://linkinghub.elsevier.com/retrieve/pii/S0085...

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https://medlineplus.gov/vasculitis.html

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https://scite.ai/reports/27914700

MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Bradykinin, Calcium, Cell Line, Cell-Derived Microparticles, Child, Endothelial Cells, Female, Flow Cytometry, Humans, Inflammation, Kidney, Kinins, Leukocytes, Male, Middle Aged, Neutrophils, Receptor, Bradykinin B1, Transfection, Vasculitis, Young Adult