title: Caffeic acid inhibits acute hyperhomocysteinemia-induced leukocyte rolling and adhesion in mouse cerebral venules.
abstract: OBJECTIVE
  To investigate the effects and possible mechanisms of CA on acute HHcy-induced leukocyte rolling and adhesion in mouse cerebral venules.
  
  
  METHODS
  Male C57 BL/6J mice were injected with DL-Hcy (50 mg/kg) and CA (10 mg/kg). The effect of CA on HHcy-induced leukocyte rolling and adhesion in cerebral vessels was assessed using intravital microscopy. Plasma cytokines and chemokines were evaluated by cytometric bead array. ROS production in HUVECs and adhesion molecule expression on leukocytes were determined by flow cytometry. E-selectin and ICAM-1 expression in cerebrovascular endothelium was detected by immunohistochemistry. CD18 phosphorylation and the Src/PI3K/Akt pathway in leukocytes were determined by confocal microscopy and Western blot.
  
  
  RESULTS
  CA inhibited HHcy-elicited leukocyte rolling and adhesion, decreased ROS production in HUVECs, and reduced plasma KC, MIP-2, and MCP-1 levels. CA reduced the E-selectin and ICAM-1 expression on cerebrovascular endothelium and CD11b/CD18 on leukocytes caused by HHcy. Of notice, CA depressed CD18 phosphorylation and the Src/PI3K/Akt pathway in leukocytes.
  
  
  CONCLUSIONS
  CA inhibited HHcy-provoked leukocyte rolling and adhesion in cerebral venules, ameliorating adhesion molecule expression and activation, which is related to the suppression of the Src/PI3K/Akt pathway in leukocytes.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wei
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Mao
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Chuan-She
authors.initials: CS
authors.lastname: Wang
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D018932:Chemokine CCL2 / Q000097:blood; D054426:Chemokine CXCL2 / Q000097:blood; D018925:Chemokines / Q000097:blood; D019040:E-Selectin / Q000096:biosynthesis; D061307:Human Umbilical Vein Endothelial Cells; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D036904:Leukocyte Rolling / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014699:Venules / Q000187:drug effects
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D002109:Caffeic Acids; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D019040:E-Selectin; C090509:Icam1 protein, mouse; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; C074302:keratinocyte-derived chemokines; C040048:caffeic acid