title: A chemokine self-presentation mechanism involving formation of endothelial surface microstructures.
abstract: Endothelial surface microstructures have been described previously under inflammatory conditions; however, they remain ill-characterized. In this study, CXCL8, an inflammatory chemokine, was shown to induce the formation of filopodia-like protrusions on endothelial cells; the same effects were observed with CXCL10 and CCL5. Chemokines stimulated filopodia formation by both microvascular (from bone marrow and skin) and macrovascular (from human umbilical vein) endothelial cells. Use of blocking Abs and degradative enzymes demonstrated that CXCL8-stimulated filopodia formation was mediated by CXCR1 and CXCR2, Duffy Ag/receptor for chemokines, heparan sulfate (HS), and syndecans. HS was present on filopodial protrusions appearing as a meshwork on the cell surface, which colocalized with CXCL8, and this glycosaminoglycan was 2,6-O- and 3-O-sulfated. Transmission electron microscopy revealed that CXCL8-stimulated filopodial and microvilli-like protrusions that interacted with leukocytes before transendothelial migration and removal of HS reduced this migration. iTRAQ mass spectrometry showed that changes in the levels of cytoskeletal, signaling, and extracellular matrix proteins were associated with CXCL8-stimulated filopodia/microvilli formation; these included tropomyosin, fascin, and Rab7. This study suggests that chemokines stimulate endothelial filopodia and microvilli formation, leading to their presentation to leukocytes and leukocyte transendothelial migration.
authors: Leopold Muller Arthritis Research Centre, Institute for Science and Technology in Medicine, Medical School, Keele University, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, United Kingdom.
authors: Catherine
authors: C
authors: Whittall
authors: Oksana
authors: O
authors: Kehoe
authors: Sophie
authors: S
authors: King
authors: Antal
authors: A
authors: Rot
authors: Angela
authors: A
authors: Patterson
authors: Jim
authors: J
authors: Middleton
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008833:Microcirculation / Q000276:immunology; D013499:Surface Properties; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology
chemical_list: D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D016209:Interleukin-8