Platelet-monocyte complexes support monocyte adhesion to endothelium by enhancing secondary tethering and cluster formation.
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.


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.


CONCLUSIONS
PMCs in the circulation might be proatherogenic, and prevention of their formation is a possible therapeutic goal.
da Costa Martins
P
P
Department of Hematology and Experimental Immunohaematology, Sanquin Research, Amsterdam, The Netherlands.
van den Berk
N
N
Ulfman
Laurien H
LH
Koenderman
L
L
Hordijk
P L
PL
Zwaginga
J J
JJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology; D001792:Blood Platelets / Q000166:cytology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D018189:Immunomagnetic Separation; D007249:Inflammation / Q000097:blood / Q000473:pathology; D019041:L-Selectin / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D009000:Monocytes / Q000166:cytology*; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D013314:Stress, Mechanical
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D010980:Platelet Membrane Glycoproteins; D019041:L-Selectin