title: C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles.
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 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.
authors.affiliation: Departments of Pediatrics and.
authors.forename: Maria
authors.initials: M
authors.lastname: Mossberg
authors.affiliation: Departments of Pediatrics and.
authors.forename: Anne-Lie
authors.initials: AL
authors.lastname: Ståhl
authors.affiliation: Departments of Pediatrics and.
authors.forename: Robin
authors.initials: R
authors.lastname: Kahn
authors.affiliation: Departments of Pediatrics and.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Kristoffersson
authors.affiliation: Departments of Pediatrics and.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Tati
authors.affiliation: Nephrology, Clinical Sciences Lund, and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Heijl
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Segelmark
authors.affiliation: Unit of Drug Target Discovery, Division of Pharmacology and Structural Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden; and.
authors.forename: L M Fredrik
authors.initials: LMF
authors.lastname: Leeb-Lundberg
authors.affiliation: Departments of Pediatrics and diana.karpman@med.lu.se.
authors.forename: Diana
authors.initials: D
authors.lastname: Karpman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055252:Cell-Derived Microparticles / Q000502:physiology*; D002633:Chemotaxis; D002648:Child; D003174:Complement C1 Inactivator Proteins / Q000502:physiology*; D050718:Complement C1 Inhibitor Protein; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014657:Vasculitis / Q000473:pathology*; D055815:Young Adult
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human
keywords: Chronic inflammation; complement; glomerular endothelial cells; kinin; neutrophils; vasculitis