Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis
2017 (English)In: KIDNEY INTERNATIONAL, ISSN 0085-2538, Vol. 91, no 1, 96-105 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2017. Vol. 91, no 1, 96-105 p.
ANCA; bradykinin; kinin receptors; microvesicles; vasculitis
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-134303DOI: 10.1016/j.kint.2016.09.023ISI: 000391162700015PubMedID: 27914700OAI: oai:DiVA.org:liu-134303DiVA: diva2:1071700
Funding Agencies|Swedish Research Council [K2013-64X-14008]; Knut and Alice Wallenberg Foundation (Wallenberg Clinical Scholar) [2015.0320]; Torsten Soderberg Foundation; Skane Centre of Excellence in Health; Konung Gustaf V:s 80-arsfond; Crown Princess Lovisas Society for Child Care; Royal Physiographic Society in Lund; Swedish Rheumatism Association; Greta and Johan Kocks Foundation; Hedberg Foundation; Fanny Ekdahl Foundation; Anna-Greta Crafoord Foundation; Swedish Medical Society; Jerring Foundation; Alfred Osterlunds Foundation2017-02-062017-02-032017-02-06