C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles.
J Am Soc Nephrol
; 28(8): 2472-2481, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-28289183
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 endothelial microvesicles may 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vasculitis
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Complement C1 Inactivator Proteins
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Cell-Derived Microparticles
Limits:
Adolescent
/
Adult
/
Aged
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Aged80
/
Child
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Am Soc Nephrol
Journal subject:
NEFROLOGIA
Year:
2017
Document type:
Article
Country of publication:
United States