title: A novel mechanism of γ/δ T-lymphocyte and endothelial activation by shear stress: the role of ecto-ATP synthase β chain.
abstract: BACKGROUND
  Endothelial cells (ECs) have distinct mechanotransduction mechanisms responding to laminar versus disturbed flow patterns. Endothelial dysfunction, affected by imposed flow, is one of the earliest events leading to atherogenesis. The involvement of γ/δ T lymphocytes in endothelial dysfunction under flow is largely unknown.
  
  
  OBJECTIVE
  To investigate whether shear stress regulates membrane translocation of ATP synthase β chain (ATPSβ) in ECs, leading to the increased γ/δ T-lymphocyte adhesion and the related functions.
  
  
  RESULTS
  We applied different flow patterns to cultured ECs. Laminar flow decreased the level of membrane-bound ATPSβ (ecto-ATPSβ) and depleted membrane cholesterol, whereas oscillatory flow increased the level of ecto-ATPSβ and membrane cholesterol. Incubating ECs with cholesterol or depleting cellular cholesterol with β-cyclodextrin mimicked the effect of oscillatory or laminar flow, respectively. Knockdown caveolin-1 by small interfering RNA prevented ATPSβ translocation in response to laminar flow. Importantly, oscillatory flow or cholesterol treatment elevated the number of γ/δ T cells binding to ECs, which was blocked by anti-ATPSβ antibody. Furthermore, the incubation of γ/δ T cells with ECs increased tumor necrosis fact α and interferon-γ secretion from T cells and vascular cell adhesion molecule-1 expression in ECs. In vivo, γ/δ T-cell adhesion and ATPSβ membrane translocation was elevated in the aortic inner curvature and disturbed flow areas in partially ligated carotid arteries of ApoE(-/-) mice fed a high-fat diet.
  
  
  CONCLUSIONS
  This study provides evidence that disturbed flow and hypercholesterolemia synergistically promote γ/δ T-lymphocyte activation by the membrane translocation of ATPSβ in ECs and in vivo in mice, which is a novel mechanism of endothelial activation.
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Sciences Center, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fu
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Hou
authors.forename: Chenglai
authors.initials: C
authors.lastname: Fu
authors.forename: Mingxia
authors.initials: M
authors.lastname: Gu
authors.forename: Chenghong
authors.initials: C
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: John Y-J
authors.initials: JY
authors.lastname: Shyy
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D051242:Caveolin 1 / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D025261:Mitochondrial Proton-Translocating ATPases / Q000502:physiology*; D023421:Models, Animal; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013314:Stress, Mechanical; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
chemical_list: C506526:ATP5F1B protein, human; D001057:Apolipoproteins E; D051242:Caveolin 1; D016692:Receptors, Antigen, T-Cell, gamma-delta; D002784:Cholesterol; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D025261:Mitochondrial Proton-Translocating ATPases