Platelet-Monocyte Complexes Support Monocyte Adhesion to Endothelium by Enhancing Secondary Tethering and Cluster Formation

P. Da Costa Martins, N. Van Den Berk, Laurien H. Ulfman, L. Koenderman, P. L. Hordijk, J. J. Zwaginga*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective-Adhesion of monocytes to endothelium can be supported by monocyte-monocyte interactions resulting in the formation of cell aggregates at the vessel wall (clusters). Since platelets that are bound to the injured vessel wall support monocyte adhesion and platelet activation in the circulation leads to formation of platelet-monocyte complexes (PMCs), we examined whether adhesion of PMCs to the vessel wall enhances monocyte clustering. Methods and Results-The effect of PMC formation in monocyte adhesion and clustering on human umbilical vein endothelial cells (HUVECs) was studied in vitro with a perfusion system. In the presence of 10% to 20% PMCs, monocyte adhesion and cluster formation to stimulated HUVECs increased 2-fold above levels obtained with pure monocytes. While the observed effects increased with higher PMC levels, blocking-monoclonal antibodies directed against platelet-associated P-selectin or monocyte P-selectin glycoprotein ligand-1 (PSGL-1) reversed adhesion and clustering to control values. In the presence of PMCs, blocking L-selectin decreased adhesion by 25%. When PMCs were present, clustering was only supported by L-selectin at higher shear. These data indicate that monocyte adhesion to the vessel wall is enhanced by PMC-mediated monocyte secondary tethering. These interactions are mainly mediated by P-selectin and PSGL-1. Conclusion-PMCs in the circulation might be proatherogenic, and prevention of their formation is a possible therapeutic goal.

Original languageEnglish
Pages (from-to)193-199
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number1
Publication statusPublished - Jan 2004

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