Advanced

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

Kahn, Robin LU ; Mossberg, Maria LU ; Ståhl, Anne lie LU ; Johansson, Karl LU ; Lopatko Lindman, Ingrid LU ; Heijl, Caroline LU ; Segelmark, Mårten LU ; Mörgelin, Matthias LU ; Leeb-Lundberg, Fredrik LU and Karpman, Diana LU (2017) In Kidney International 91(1). p.96-105
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ANCA, bradykinin, kinin receptors, microvesicles, vasculitis
in
Kidney International
volume
91
issue
1
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85006380317
  • wos:000391162700015
ISSN
0085-2538
DOI
10.1016/j.kint.2016.09.023
language
English
LU publication?
yes
id
5bdc5162-5a2c-4e3c-827d-2becddc39382
date added to LUP
2017-01-13 13:56:47
date last changed
2018-05-29 11:14:49
@article{5bdc5162-5a2c-4e3c-827d-2becddc39382,
  abstract     = {<p>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.</p>},
  author       = {Kahn, Robin and Mossberg, Maria and Ståhl, Anne lie and Johansson, Karl and Lopatko Lindman, Ingrid and Heijl, Caroline and Segelmark, Mårten and Mörgelin, Matthias and Leeb-Lundberg, Fredrik and Karpman, Diana},
  issn         = {0085-2538},
  keyword      = {ANCA,bradykinin,kinin receptors,microvesicles,vasculitis},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {96--105},
  publisher    = {Nature Publishing Group},
  series       = {Kidney International},
  title        = {Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis},
  url          = {http://dx.doi.org/10.1016/j.kint.2016.09.023},
  volume       = {91},
  year         = {2017},
}