Please use this identifier to cite or link to this item: http://buratest.brunel.ac.uk/handle/2438/9825
Title: Soluble gC1qR is an autocrine signal that induces B1R expression on endothelial cells
Authors: Ghebrehiwet, B
Ji, Y
Valentino, A
Pednekar, L
Ramadass, M
David, H
Kew, RR
Hosszu, KH
Galanakis, DK
Kishore, U
Peerschke, EIB
Keywords: Bradykinin (BK);C1q receptor;sgC1qR
Issue Date: 2014
Citation: Journal of Immunology, 192(1): pp.377 - 384, (2014)
Abstract: Bradykinin (BK) is one of the most potent vasodilator agonists known and belongs to the kinin family of proinflammatory peptides. BK induces its activity via two G protein-coupled receptors: BK receptor 1 (B1R) and BK receptor 2. Although BK receptor 2 is constitutively expressed on endothelial cells (ECs), B1R is induced by IL-1β. The C1q receptor, receptor for the globular heads of C1q (gC1qR), which plays a role in BK generation, is expressed on activated ECs and is also secreted as soluble gC1qR (sgC1qR). Because sgC1qR can bind to ECs, we hypothesized that it may also serve as an autocrine/paracrine signal for the induction of B1R expression. In this study, we show that gC1qR binds to ECs via a highly conserved domain consisting of residues 174-180, as assessed by solid-phase binding assay and deconvolution fluorescence microscopy. Incubation of ECs (24 h, 37°C) with sgC1qR resulted in enhancement of B1R expression, whereas incubation with gC1qR lacking aa 174-180 and 154-162 had a diminished effect. Binding of sgC1qR to ECs was through surface-bound fibrinogen and was inhibited by anti-fibrinogen. In summary, our data suggest that, at sites of inflammation, sgC1qR can enhance vascular permeability by upregulation of B1R expression through de novo synthesis, as well as rapid translocation of preformed B1R.
URI: http://www.jimmunol.org/content/192/1/377
http://bura.brunel.ac.uk/handle/2438/9825
DOI: http://dx.doi.org/10.4049/jimmunol.1302031
ISSN: 0022-1767
Appears in Collections:Dept of Clinical Sciences Research Papers

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