Abstract 3914: The Novel Identified Platelet Receptor Emmprin (CD147/Basigin) Induces Platelet-Monocyte Interaction In Vivo And Augments Monocyte Recruitment To The Vascular Wall
Platelets play a central role in the hemostatic process, thrombus formation and in inflammation processes. In inflammation platelets interact with EC and monocytes and are suggested to enhance leukocyte recruitment into vascular wall. The Extracellular Matrix Metalloproteinase Inducer (EMMPRIN/Basigin) was first identified on tumor cells and is involved in MMP synthesis by a homophilic interaction. We recently identified an increased surface expression of EMMPRIN on monocytes in acute myocardial infarction and an activation dependant expression of EMMPRIN on platelets. Also, platelet-monocyte interactions via EMMPRIN stimulate NFkB-driven inflammatory pathways in monocytes in vitro. No effect of this novel receptor for platelet-monocyte interactions or cellular recruitment in vivo was described so far.
Methods and results: In a laminar flow assay freshly isolated platelets were allowed to adhere to collagen coated cover slips, afterwards firm adhesion of human isolated monocytes to the immobilized and activated platelets was measured under arterial flow conditions. Pre-treatment of monocytes with an activity-blocking anti-EMMPRIN monoclonal antibody substantially attenuated monocyte firm adhesion (42.17 ± 8.67 control vs. 12.24 ± 2.79 mAb, cells per high powerfield, n=4, p<0.05). Similar results could be demonstrated after gene silencing of EMMPRIN by small-interfering RNA in monocytes (34.36 ± 6,78 control vs. 12.57 ± 5,04 siRNA, cells per high powerfield, n=3, p<0.05). In vivo gene silencing of Basigin in mouse monocytic cells decreased formation of monocyte-platelet aggregates by 57.86 ±18.17 % as compared to control siRNA (n=3, p<0.05). The use of intravital video-fluorescence microscopy revealed that siRNA mediated inhibition of basigin surface expression in monocytes inhibits recruitment of monocytes to the arterial wall after endothelial denudation (179.8 ± 34.6 cells/mm2 control siRNA vs. 59.2 ± 26.3 cells/mm2 basigin siRNA n=8, p<0.05).
Conclusion: The novel identified receptor EMMPRIN supports platelet-monocyte interaction in vivo and promotes monocyte recruitment to the arterial wall. Therefore EMMPRIN might represent an a novel target to reduce the burden of protease activity and inflammation in atherosclerosis.