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C1-inhibitor decreases the release of vasculitis-like chemotactic endothelial microvesicles

Mossberg, Maria LU ; Ståhl, Anne Lie LU ; Kahn, Robin LU ; Kristoffersson, Ann Charlotte LU ; Tati, Ramesh LU ; Heijl, Caroline LU ; Segelmark, Mårten LU ; Leeb-Lundberg, Fredrik LU and Karpman, Diana LU (2017) In Journal of the American Society of Nephrology : JASN 28(8). p.2472-2481
Abstract

The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P<0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil... (More)

The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P<0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor.We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor-depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelialmicrovesiclesmay contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Society of Nephrology : JASN
volume
28
issue
8
pages
10 pages
external identifiers
  • scopus:85026503776
  • wos:000406570500021
ISSN
1046-6673
DOI
10.1681/ASN.2016060637
language
English
LU publication?
yes
id
c18bda42-1568-42e8-a54f-75dcff3dcd41
date added to LUP
2017-08-21 14:47:00
date last changed
2017-09-18 11:42:24
@article{c18bda42-1568-42e8-a54f-75dcff3dcd41,
  abstract     = {<p>The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P&lt;0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor.We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor-depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelialmicrovesiclesmay contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation.</p>},
  author       = {Mossberg, Maria and Ståhl, Anne Lie and Kahn, Robin and Kristoffersson, Ann Charlotte and Tati, Ramesh and Heijl, Caroline and Segelmark, Mårten and Leeb-Lundberg, Fredrik and Karpman, Diana},
  issn         = {1046-6673},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {2472--2481},
  series       = {Journal of the American Society of Nephrology : JASN},
  title        = {C1-inhibitor decreases the release of vasculitis-like chemotactic endothelial microvesicles},
  url          = {http://dx.doi.org/10.1681/ASN.2016060637},
  volume       = {28},
  year         = {2017},
}