title: Soluble gC1qR is an autocrine signal that induces B1R expression on endothelial cells.
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.
authors: Department of Medicine, Stony Brook University, Stony Brook, NY 11794;
authors: Berhane
authors: B
authors: Ghebrehiwet
authors: Yan
authors: Y
authors: Ji
authors: Alisa
authors: A
authors: Valentino
authors: Lina
authors: L
authors: Pednekar
authors: Mahalakshmi
authors: M
authors: Ramadass
authors: David
authors: D
authors: Habiel
authors: Richard R
authors: RR
authors: Kew
authors: Kinga H
authors: KH
authors: Hosszu
authors: Dennis K
authors: DK
authors: Galanakis
authors: Uday
authors: U
authors: Kishore
authors: Ellinor I B
authors: EI
authors: Peerschke
mesh_terms: D019898:Autocrine Communication / Q000187:drug effects; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D043783:Receptor, Bradykinin B1; D005340:Fibrinogen