PMID- 15271798
OWN - NLM
STAT- MEDLINE
DCOM- 20041223
LR  - 20220408
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 104
IP  - 10
DP  - 2004 Nov 15
TI  - The contribution of endothelial cell P-selectin to the microvascular flow of 
      mouse sickle erythrocytes in vivo.
PG  - 3378-85
AB  - Microvascular occlusion in sickle cell disease can be initiated by adhesion of 
      sickle red blood cells (RBCs) to the endothelium. Our objective in this study was 
      to verify the relevance in vivo of our discovery that sickle RBCs adhere 
      abnormally to endothelial P-selectin in vitro. We used computer-assisted 
      intravital microscopy to characterize RBC flow velocity (V(RBC)) in mice. We 
      found faster V(RBC) of sickle RBCs in P-selectin knock-out and control mice than 
      in sickle cell mice, which have increased endothelial cell P-selectin expression. 
      Agonist peptide for murine protease-activated receptor-1 (PAR-1), which 
      selectively activates mouse endothelial cells but not platelets, was used to 
      assess the effects of endothelial cell P-selectin on microvascular flow. 
      Suffusion of venules with this agonist stopped flow promptly in normal and sickle 
      mice but not in P-selectin knock-out mice or in control mice pretreated with 
      anti-P-selectin monoclonal antibody or unfractionated heparin (UFH). 
      Agonist-induced slowing of flow was reversed rapidly by suffusion with UFH, 
      provided flow had not already stopped. We conclude that endothelial cell 
      P-selectin contributes to the microcirculatory abnormalities in sickle cell 
      disease and that blocking P-selectin may be useful for preventing painful 
      vasoocclusion in sickle cell disease.
FAU - Embury, Stephen H
AU  - Embury SH
AD  - Department of Medicine, University of San Francisco, CA, USA. 
      sembury@itsa.ucsf.edu.
FAU - Matsui, Neil M
AU  - Matsui NM
FAU - Ramanujam, Sahana
AU  - Ramanujam S
FAU - Mayadas, Tanya N
AU  - Mayadas TN
FAU - Noguchi, Constance T
AU  - Noguchi CT
FAU - Diwan, Bhalchandra A
AU  - Diwan BA
FAU - Mohandas, Narla
AU  - Mohandas N
FAU - Cheung, Anthony T W
AU  - Cheung AT
LA  - eng
GR  - HL64396/HL/NHLBI NIH HHS/United States
GR  - HL67432/HL/NHLBI NIH HHS/United States
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
GR  - HL20985/HL/NHLBI NIH HHS/United States
GR  - HL31579/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040722
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (P-Selectin)
RN  - 0 (Receptor, PAR-1)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Anemia, Sickle Cell/*metabolism/*physiopathology
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Blood Flow Velocity
MH  - Cell Adhesion
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Erythrocytes/cytology/*physiology
MH  - Heparin/analogs & derivatives
MH  - Leukocytes/cytology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Microcirculation
MH  - P-Selectin/immunology/*metabolism
MH  - Receptor, PAR-1/agonists/metabolism
EDAT- 2004/07/24 05:00
MHDA- 2004/12/24 09:00
CRDT- 2004/07/24 05:00
PHST- 2004/07/24 05:00 [pubmed]
PHST- 2004/12/24 09:00 [medline]
PHST- 2004/07/24 05:00 [entrez]
AID - S0006-4971(20)55904-1 [pii]
AID - 10.1182/blood-2004-02-0713 [doi]
PST - ppublish
SO  - Blood. 2004 Nov 15;104(10):3378-85. doi: 10.1182/blood-2004-02-0713. Epub 2004 
      Jul 22.