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The urokinase receptor (urokinase plasminogen activator receptor; uPAR) regulates monocyte adhesion by direct binding to vitronectin and by forming complexes with integrins. Therefore, possible up-regulation of uPAR in acute myocardial infarction (AMI) may affect monocyte adhesion. In 20 patients with AMI, uPAR surface expression (measured by flow cytometry) was increased compared with that in patients with chronic stable angina (mean +/- SD fluorescence, 179 +/- 96 vs 80 +/- 53; P =.002). Expression of uPAR correlated with activation of beta(2)-integrins lymphocyte function-associated antigen 1 (LFA-1) and macrophage antigen 1 (Mac-1), measured by using monoclonal antibodies (mAbs) 24 and CBRM1/5. Isolated mononuclear cells (MNCs) from patients with AMI showed enhanced adhesiveness to human umbilical vein endothelial cells (HUVECs), to fibrinogen (Mac-1 ligand), and to vitronectin (uPAR ligand). Excessive adhesion of MNCs to HUVECs was inhibited by mAbs anti-CD18 (84%), anti-CD11a (51%), and anti-CD11b (57%), indicating a major contribution of LFA-1 and Mac-1. The mAb anti-uPAR R3 blocked adhesion of cells from patients with AMI to vitronectin (95%) but also beta(2)-integrin-mediated adhesion to fibrinogen (79%) and HUVECs (66%). Incubation of monocytic MonoMac6 cells with plasma from patients with AMI enhanced uPAR messenger RNA expression and cell adhesion to HUVECs. Thus, released soluble factors may contribute to enhanced monocyte adhesion in AMI. Mouse pre-B lymphocytes (BAF3 cells) transfected with various amounts of uPAR complementary DNA showed a strong correlation of uPAR expression with beta(2)-integrin-dependent adhesion to intercellular adhesion molecule 1, thus providing evidence for the functional relevance of uPAR up-regulation in an isolated in vitro system. In conclusion, we found that uPAR expression is elevated on monocytes in AMI and contributes to enhanced cell adhesion. Thus, uPAR may be a novel target for prevention of unwanted monocyte recruitment as part of inflammatory cardiovascular processes.
May et al. (Wed,) studied this question.