Abstract 991: EMMPRIN (CD 147): A Novel Identified Receptor on Platelets Induces Cell Activation, Mediates Platelet Rolling and Amplifies Monocytic MMP-9 Activity at Monocytic-Platelet Interactions
Platelets play a pivotal role in the hemostatic process, thrombus formation and in inflammation processes. In inflammation platelets interact with EC and monocytes leading to enhanced leukocyte recruitment into vascular wall. The Extracellular Matrix Metalloproteinase Inducer (EMMPRIN/CD 147) was first identified on tumor cells and is involved in MMP synthesis by yet unknown mechanisms. On monocytes, EC and SMCs surface expression of EMMPRIN is dependent on cellular activation. We recently identified an increased surface expression of EMMPRIN on monocytes in acute myocardial infarction. No expression of EMMPRIN on platelets was described so far.
Methods and results: Freshly isolated, non stimulated platelets nearly showed no surface expression of EMMPRIN. Stimulation with thrombin (0.1 and 1 U/ml, 1h) or with ADP (5μmolar, 1h) upregulated EMMPRIN surface expression [flow cytometry, western blot, fluorescence microscopy]. Electron microscopy revealed EMMPRIN to be located within the open canalicular system. Moreover incubation of platelets with recombinant Fc-EMMPRIN (10μg/mL, 1h) induced enhanced surface expression of CD 40L and CD 62P (P-selectin) as compared to Fc [n=8; mean fluorescence anti-CD40L: 24.5±5.2 vs. 4.2±4.0; anti-CD62P 22.8±3.3 vs. 8.5±6.5; flow cytometry). Furthermore substantial increase of platelet tethering to Fc-EMMPRIN under high shear stress (2000s−1) in vitro was noted as compared to adhesion to Fc as negative control. Moreover recombinant platelets with enhanced EMMPRIN surface expression amplified MMP-9 activity of monocytes during cellular interactions as compared to coincubation with control platelets [SDS page zymography, n=5].
Conclusion: EMMPRIN is a novel identified platelet receptor which is upregulated on stimulated platelets. EMMPRIN-EMMPRIN signalling leads to platelet activation with enhanced surface expression of CD 40L and P-selectin. EMMPRIN mediates platelet rolling under high shear stress in vitro. Finally EMMPRIN mediates MMP-9 activation at platelet-monocyte interaction.