title: Oligomerized, filamentous surface presentation of RANTES/CCL5 on vascular endothelial cells.
abstract: Vascular endothelial cells present luminal chemokines that arrest rolling leukocytes by activating integrins. It appears that several chemokines must form higher-order oligomers to elicit proper in vivo effects, as mutants restricted to forming dimers have lost the ability to recruit leukocytes to sites of inflammation. Here, we show for the first time that the chemokine RANTES/CCL5 binds to the surface of human endothelial cells in a regular filamentous pattern. Furthermore, the filaments bound to the surface in a heparan sulfate-dependent manner. By electron microscopy we observed labeling for RANTES on membrane projections as well as on the remaining plasma membrane. Mutant constructs of RANTES restricted either in binding to heparin, or in forming dimers or tetramers, appeared either in a granular, non-filamentous pattern or were not detectable on the cell surface. The RANTES filaments were also present after exposure to flow, suggesting that they can be present in vivo. Taken together with the lacking in vivo or in vitro effects of RANTES mutants, we suggest that the filamentous structures of RANTES may be of physiological importance in leukocyte recruitment.
authors: 1] Department of Pathology, Oslo University Hospital and University of Oslo, PO Box 4950 Nydalen, N-0424 Oslo, Norway [2] Centre for Immune Regulation, University of Oslo, RikshospitaletPO Box 4950 Nydalen, N-0424 Oslo, Norway.
authors: Inger
authors: I
authors: Øynebråten
authors: The Department of Biosciences, University of Oslo, PO Box 1041 Blindern, 0316 N-Oslo, Norway.
authors: Nicolas
authors: N
authors: Barois
authors: The Department of Biosciences, University of Oslo, PO Box 1041 Blindern, 0316 N-Oslo, Norway.
authors: Trygve
authors: T
authors: Bergeland
authors: Department of Pathology, Oslo University Hospital and University of Oslo, PO Box 4950 Nydalen, N-0424 Oslo, Norway.
authors: Axel M
authors: AM
authors: Küchler
authors: 1] Centre for Immune Regulation, University of Oslo, RikshospitaletPO Box 4950 Nydalen, N-0424 Oslo, Norway [2] The Department of Biosciences, University of Oslo, PO Box 1041 Blindern, 0316 N-Oslo, Norway.
authors: Oddmund
authors: O
authors: Bakke
authors: 1] Department of Pathology, Oslo University Hospital and University of Oslo, PO Box 4950 Nydalen, N-0424 Oslo, Norway [2] K. G. Jebsen Inflammation Research Centre, University of Oslo, RikshospitaletPO Box 4950 Nydalen, N-0424 Oslo, Norway.
authors: Guttorm
authors: G
authors: Haraldsen
mesh_terms: D001704:Biopolymers / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006497:Heparan Sulfate / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001704:Biopolymers; D018946:Chemokine CCL5; D006497:Heparan Sulfate; D007371:Interferon-gamma; D014409:Tumor Necrosis Factor-alpha; C483024:CCL5 protein, human