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)
- author
- 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
- organization
- publishing date
- 2017-01-01
- 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
- pmid:27914700
- 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
- 2024-04-05 14:38:28
@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}},
keywords = {{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}},
doi = {{10.1016/j.kint.2016.09.023}},
volume = {{91}},
year = {{2017}},
}