Regulation of CD11b/CD18 (Mac-1) adhesion to fibrinogen by urokinase receptor (uPAR).
OBJECTIVE
The goal of this study is to investigate the consequence of the interaction between Mac-1 and uPAR and determine the mechanisms by which uPAR regulates Mac-1 dependent adhesion to fibrinogen.


METHODS
Human embryonic kidney 293 cells transfected with Mac-1 or uPAR or co-transfected with both Mac-1 and uPAR.


METHODS
Cell adhesion and binding assays and Western Blotting for protein tyrosine phosphorylation analysis.


RESULTS
The adhesion to fibrinogen was increased two-fold for Mac-1-uPAR co-transfected cells comparing to the Mac-1 transfected cells alone. The increased adhesion was inhibited when cells were treated with phosphatidylinositol-specific phospholipase C to remove uPAR. Occupancy of uPAR with urokinase-type plasminogen activator further enhanced the cell adhesion to fibrinogen. Phosphorylation of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) was increased in Mac-1-uPAR co-transfected cells but not in Mac-1 transfected cells.


CONCLUSIONS
uPAR up-regulated the Mac-1 adhesion to fibrinogen and FAK and MAPK were involved in this regulation.
Zhang
H
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The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
Colman
R W
RW
Sheng
N
N
D039481:CD11b Antigen / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D039481:CD11b Antigen; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator