Regulation of CD11b/CD18 (Mac-1) adhesion to fibrinogen by urokinase receptor (uPAR)

Abstract:

Objective and Design: 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.¶Material: 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.