Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Urokinase Receptor Surface Expression Regulates Monocyte Adhesion in Acute Myocardial Infarction

Abstract

The urokinase receptor (uPAR) regulates monocyte adhesion by direct binding to vitronectin and by forming complexes with integrins. Potential upregulation of uPAR in acute myocardial infarction (AMI) may, therefore, affect monocyte adhesion. In 20 patients with AMI uPAR surface expression (measured by flow cytometry) was increased as compared to patients with chronic stable angina (CSA) (179±96 vs. 80±53, mean fluorescence±SD, p=0.002). uPAR expression correlated with activation of ß2-integrins LFA-1 and Mac-1, measured by mAbs 24 and CBRM1/5. Isolated mononuclear cells (MNC) from patients with AMI showed enhanced adhesivity to endothelial cells (HUVEC), to fibrinogen (Mac-1-ligand) and to vitronectin (uPAR-ligand). Excessive adhesion of MNC to HUVEC was inhibited by mAbs anti-CD18 (84%), anti-CD11a (51%) or anti-CD11b (57%), indicating a major contribution of LFA-1 and Mac-1. MAb anti-uPAR R3 blocked adhesion of cells from AMI-patients to vitronectin (95%) but also ß2-integrin-mediated adhesion to fibrinogen (79%) or HUVEC (66%). Incubation of monocytic MonoMac6 cells with AMI-plasma enhanced uPAR mRNA expression and cell adhesion to HUVEC. Thus, released soluble factors may contribute to enhanced monocyte adhesion in AMI. Mouse pre-B-lymphocytes (BAF3-cells), transfected with various amounts of uPAR-cDNA, showed strong correlation of uPAR expression with [beta]2-integrin-dependent adhesion to ICAM-1, thus providing evidence for the functional relevance of uPAR upregulation in an isolated in vitro system. In conclusion, uPAR expression is elevated on monocytes in AMI and contributes to enhanced cell adhesion. Thus, uPAR may present a novel target for prevention of unwanted monocyte recruitment as part of inflammatory cardiovascular processes.