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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Kahn R,Mossberg M,Ståhl AL,Johansson K,Lopatko Lindman I,Heijl C,Segelmark M,Mörgelin M,Leeb-Lundberg LM,Karpman D

doi

10.1016/j.kint.2016.09.023

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

96-105

issue

1

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(16)30552-X

journal_volume

91

pub_type

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