title: Contribution of platelet CX(3)CR1 to platelet-monocyte complex formation and vascular recruitment during hyperlipidemia.
abstract: OBJECTIVE
  The chemokine receptor CX(3)CR1 is an inflammatory mediator in vascular diseases. On platelets, its ligation with fractalkine (CX(3)CL1) induces platelet activation followed by leukocyte recruitment to activated endothelium. Here, we evaluated the expression and role of platelet-CX(3)CR1 during hyperlipidemia and vascular injury.
  
  
  RESULTS
  The existence of CX(3)CR1 on platelets at mRNA and protein level was analyzed by RT-PCR, quantitative (q)PCR, FACS analysis, and Western blot. Elevated CX(3)CR1 expression was detected on human platelets after activation and, along with increased binding of CX(3)CL1, platelet CX(3)CR1 was also involved in the formation of platelet-monocyte complexes. Interestingly, the expression of CX(3)CR1 was elevated on platelets from hyperlipidemic mice. Accordingly, CX(3)CL1-binding and the number of circulating platelet-monocyte complexes were increased. In addition, CX(3)CR1 supported monocyte arrest on inflamed smooth muscle cells in vitro, whereas CX(3)CR1-deficient platelets showed decreased adhesion to the denuded vessel wall in vivo.
  
  
  CONCLUSIONS
  Platelets in hyperlipidemic mice display increased CX(3)CR1-expression and assemble with circulating monocytes. The formation of platelet-monocyte complexes and the detection of platelet-bound CX(3)CL1 on inflamed smooth muscle cells suggest a significant involvement of the CX(3)CL1-CX(3)CR1 axis in platelet accumulation and monocyte recruitment at sites of arterial injury in atherosclerosis.
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Otilia
authors.initials: O
authors.lastname: Postea
authors.forename: Elena M
authors.initials: EM
authors.lastname: Vasina
authors.forename: Sandra
authors.initials: S
authors.lastname: Cauwenberghs
authors.forename: Delia
authors.initials: D
authors.lastname: Projahn
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Dirk
authors.initials: D
authors.lastname: Lievens
authors.forename: Wendy
authors.initials: W
authors.lastname: Theelen
authors.forename: Birgit K
authors.initials: BK
authors.lastname: Kramp
authors.forename: Elena D
authors.initials: ED
authors.lastname: Butoi
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Rory R
authors.initials: RR
authors.lastname: Koenen
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D000073883:CX3C Chemokine Receptor 1; D002460:Cell Line; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015498:HIV-2; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism*; D015539:Platelet Activation; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics*; D015728:Receptors, HIV / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000073883:CX3C Chemokine Receptor 1; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV