TY - JOUR
T1 - F11-receptor (F11R/JAM) mediates platelet adhesion to endothelial cells
T2 - Role in inflammatory thrombosis
AU - Babinska, Anna
AU - Kedees, Mamdouh H.
AU - Athar, Humra
AU - Ahmed, Tahir
AU - Batuman, Olcay
AU - Ehrlich, Yigal H.
AU - Hussain, M. Mahmood
AU - Kornecki, Elizabeth
PY - 2002/11/1
Y1 - 2002/11/1
N2 - The F11 receptor (F11R) is a cell adhesion molecule (CAM), member of the immunoglobulin superfamily found on the surface of human platelets, and determined to play a role in platelet aggregation, secretion, adhesion and spreading. The same molecule is present also at tight junctions of endothelial cells (EC) where it is known as JAM and acts as a CAM through homophilic interactions. The role of F11R/JAM in the interaction of platelets with endothelial cells was investigated in the current studies. We report here that washed human platelets adhere specifically to a matrix made of immobilized, recombinant sF11R. Furthermore, platelets adhere to cytokine- (TNF-α, INF-γ) stimulated human umbilical vein endothelial cells (HUVEC), and approximately 40-60% of the adhesive force is exerted by homophilic interactions between the F11R of platelets and EC. This is evidenced by the inhibition of platelet adhesion to endothelial cells by recombinant soluble form of the F11R, and by two F11R peptides with amino acid sequences of the N-terminal region, and in the 1st Ig fold of the F11R, respectively. This study suggests a role for F11R in the adhesion of platelets to cytokine-inflamed endothelial cells and thus in thrombosis and atherosclerosis induced in non-denuded blood vessels by inflammatory processes. Agents that block the F11R-mediated adhesion of platelets to EC may be of therapeutic value in controlling thrombosis and preventing heart attacks and stroke.
AB - The F11 receptor (F11R) is a cell adhesion molecule (CAM), member of the immunoglobulin superfamily found on the surface of human platelets, and determined to play a role in platelet aggregation, secretion, adhesion and spreading. The same molecule is present also at tight junctions of endothelial cells (EC) where it is known as JAM and acts as a CAM through homophilic interactions. The role of F11R/JAM in the interaction of platelets with endothelial cells was investigated in the current studies. We report here that washed human platelets adhere specifically to a matrix made of immobilized, recombinant sF11R. Furthermore, platelets adhere to cytokine- (TNF-α, INF-γ) stimulated human umbilical vein endothelial cells (HUVEC), and approximately 40-60% of the adhesive force is exerted by homophilic interactions between the F11R of platelets and EC. This is evidenced by the inhibition of platelet adhesion to endothelial cells by recombinant soluble form of the F11R, and by two F11R peptides with amino acid sequences of the N-terminal region, and in the 1st Ig fold of the F11R, respectively. This study suggests a role for F11R in the adhesion of platelets to cytokine-inflamed endothelial cells and thus in thrombosis and atherosclerosis induced in non-denuded blood vessels by inflammatory processes. Agents that block the F11R-mediated adhesion of platelets to EC may be of therapeutic value in controlling thrombosis and preventing heart attacks and stroke.
KW - Adhesion
KW - F11R peptides
KW - Human platelet F11 receptor (F11R)
KW - HUVEC
KW - Junctional adhesion molecule (JAM)
KW - Platelet aggregation
UR - http://www.scopus.com/inward/record.url?scp=0036851155&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036851155&partnerID=8YFLogxK
U2 - 10.1055/s-0037-1613312
DO - 10.1055/s-0037-1613312
M3 - Article
C2 - 12428104
AN - SCOPUS:0036851155
VL - 88
SP - 843
EP - 850
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 5
ER -