PMID- 21629176
OWN - NLM
STAT- MEDLINE
DCOM- 20110929
LR  - 20171116
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 92
IP  - 2
DP  - 2011 Jul 27
TI  - Adenosine diphosphate receptor P2Y12-mediated migration of host smooth 
      muscle-like cells and leukocytes in the development of transplant 
      arteriosclerosis.
PG  - 148-54
LID - 10.1097/TP.0b013e318221d407 [doi]
AB  - BACKGROUND: We have recently reported that platelet P2Y12 receptors may play a 
      role in the development of transplant arteriosclerosis (TA). In the present 
      study, we investigated the role of P2Y12 receptors on host-derived smooth 
      muscle-like cells (SMLCs, including bone-marrow-derived SMLCs) and CD45+ 
      leukocytes, both of which are believed to be associated with the development of 
      TA, using P2Y12-deficient (KO) mice. METHODS: Orthotopic carotid artery 
      transplantation was performed from C3H/He (H-2k) donors into KO or wild-type (WT) 
      recipient mice (129S:C57BL/6, H-2b). Grafts were harvested at 8 weeks after 
      transplantation for histology. Plasma monocyte chemoattractant protein-1 (MCP-1) 
      levels were analyzed with a kit. Cell migration was examined using a Boyden 
      chamber system. The expression of MCP-1 messenger RNA was assessed by real-time 
      polymerase chain reaction. RESULTS: Eight weeks after allotransplantation, KO 
      recipient mice showed a significant reduction of luminal occlusion, host-derived 
      SMLCs, CD45+ leukocytes, MCP-1+ cells in the grafts, and of plasma MCP-1 levels. 
      In addition, the migration of host-derived SMLCs (including bone-marrow-derived 
      SMLCs) and CD45+ leukocytes stimulated with adenosine diphosphate (ADP) or 
      2-methylthio-ADP (2MeSADP, a stable ADP analog) was significantly decreased in KO 
      mice. There were no significant changes in MCP-1-induced cell migration between 
      WT and KO mice. The low concentration of 2MeSADP plus MCP-1 significantly 
      increased cell migration in WT but not KO mice. Furthermore, 2MeSADP-induced 
      MCP-1 messenger RNA expression was significantly reduced in the cells of KO mice. 
      CONCLUSIONS: Thus, the P2Y12-mediated migration of host-derived SMLCs and CD45+ 
      leukocytes may play an important role in the development of TA, partly by MCP-1 
      pathways.
FAU - Harada, Kosuke
AU  - Harada K
AD  - Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu 
      City, Shizuoka, Japan.
FAU - Matsumoto, Yuji
AU  - Matsumoto Y
FAU - Umemura, Kazuo
AU  - Umemura K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (P2ry12 protein, mouse)
RN  - 0 (Receptors, Purinergic P2Y12)
RN  - 0 (Thionucleotides)
RN  - 34983-48-7 (methylthio-ADP)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - EC 3.1.3.48 (Ptprc protein, mouse)
SB  - IM
MH  - Adenosine Diphosphate/analogs & derivatives/pharmacology
MH  - Animals
MH  - Arteriosclerosis/pathology/*physiopathology
MH  - Bone Marrow/pathology
MH  - Carotid Arteries/pathology/physiopathology/*transplantation
MH  - Cell Movement/*physiology
MH  - Chemokine CCL2/metabolism
MH  - Leukocyte Common Antigens/metabolism
MH  - Leukocytes/drug effects/*pathology/physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Muscle, Smooth, Vascular/drug effects/*pathology/physiopathology
MH  - Receptors, Purinergic P2Y12/deficiency/genetics/*physiology
MH  - Signal Transduction/physiology
MH  - Thionucleotides/pharmacology
EDAT- 2011/06/02 06:00
MHDA- 2011/10/01 06:00
CRDT- 2011/06/02 06:00
PHST- 2011/06/02 06:00 [entrez]
PHST- 2011/06/02 06:00 [pubmed]
PHST- 2011/10/01 06:00 [medline]
AID - 10.1097/TP.0b013e318221d407 [doi]
PST - ppublish
SO  - Transplantation. 2011 Jul 27;92(2):148-54. doi: 10.1097/TP.0b013e318221d407.