Down-regulation of integrin α M β 2 ligand-binding function by the urokinase-type plasminogen activator receptor

The cell adhesion molecule integrin α M β 2 associates with the urokinase-type plasminogen activator receptor (uPAR) on monocytes and neutrophils. uPAR also associates with members of the β 1 and β 3 integrins, and it modulates the ligand-binding function of these integrins. In this study, we showed that co-expressing uPAR with α M β 2 in 293 transfectants down-regulated the ligand-binding capacity of α M β 2 to denatured protein, fibrinogen, and intercellular adhesion molecule 1 (ICAM-1). Migration of transfectants on fibrinogen mediated by α M β 2 was reduced in the presence of uPAR. In addition, the constitutive ligand-binding property of an α M β 2 mutant was attenuated by its association with uPAR. Co-immunoprecipitation analyses using a panel of α M β 2- specific mAbs suggest shielding of the ligand-recognition site of α M β 2 by uPAR.