title: Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis.
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.
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Kahn
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Mossberg
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Anne-Lie
authors.initials: AL
authors.lastname: Ståhl
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Johansson
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lopatko Lindman
authors.affiliation: Department of Nephrology, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Heijl
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Segelmark
authors.affiliation: Department of Infection Medicine, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Unit of Drug Target Discovery, Division of Pharmacology and Structural Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: L M Fredrik
authors.initials: LM
authors.lastname: Leeb-Lundberg
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address: diana.karpman@med.lu.se.
authors.forename: Diana
authors.initials: D
authors.lastname: Karpman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001920:Bradykinin / Q000378:metabolism*; D002118:Calcium; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002648:Child; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D007705:Kinins; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014657:Vasculitis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007705:Kinins; D043783:Receptor, Bradykinin B1; D001920:Bradykinin; D002118:Calcium
keywords: ANCA; bradykinin; kinin receptors; microvesicles; vasculitis