The cell adhesion molecule integrin alpha(M)beta(2) associates with the urokinase-type plasminogen activator receptor (uPAR) on monocytes and neutrophils. uPAR also associates with members of the beta(1) and beta(3) integrins, and it modulates the ligand-binding function of these integrins. In this study, we showed that co-expressing uPAR with alpha(M)beta(2) in 293 transfectants down-regulated the ligand-binding capacity of alpha(M)beta(2) to denatured protein, fibrinogen, and intercellular adhesion molecule I (ICAM-1). Migration of transfectants on fibrinogen mediated by alpha(M)beta(2) was reduced in the presence of uPAR. In addition, the constitutive ligand-binding property of an alpha(M)beta(2) mutant was attenuated by its association with uPAR. Co-immunoprecipitation analyses using a panel of alpha(M)beta(2)-specific mAbs suggest shielding of the ligand-recognition site Of 942 by uPAR. (c) 2006 Elsevier Inc. All rights reserved.