title: Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of beta1 and beta2 integrins.
abstract: Human monocytes adhere to activated platelets, resulting in the formation of platelet-monocyte complexes (PMC). Complex formation depends on the interaction between platelet-displayed P-selectin and the specific ligand for P-selectin on leukocytes, P-selectin glycoprotein ligand-1 (PSGL-1). We have recently shown that monocytes within PMC have increased adhesive capacity to the activated endothelium. To better understand the effect of platelet binding on the capacity of monocytes to adhere to activated endothelium, the P-selectin-PSGL-1 interaction-induced changes in integrin functionality were studied. The binding of platelets to monocytes via P-selectin-PSGL-1 interactions was shown to increase expression and activity of alpha4beta1 and alphaMbeta2integrin, with a concomitant decrease in L-selectin expression. Furthermore, the binding of platelets to monocytes resulted in increased monocyte adhesion to intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and fibronectin. Platelet binding was also responsible for an increase in monocyte transendothelial migration. Similar effects were observed after engagement of PSGL-1 with specific antibodies or with P-selectin immunoglobulin protein. Our data suggest that platelets, by binding via P-selectin to PSGL-1 on monocytes, induce up-regulation and activation of beta1 and beta2integrins and increased adhesion of monocytes to activated endothelium. Hence, monocytes within PMC are in a higher state of activation and may have, therefore, an increased atherogenic capacity.
authors.affiliation: Dept. of Experimental Immunohematology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands. p.martinsdacosta@sanquin.nl
authors.forename: Paula A
authors.initials: PA
authors.lastname: da Costa Martins
authors.forename: Janine M
authors.initials: JM
authors.lastname: van Gils
authors.forename: Anita
authors.initials: A
authors.lastname: Mol
authors.forename: Peter L
authors.initials: PL
authors.lastname: Hordijk
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Zwaginga
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D018821:CD18 Antigens; D005353:Fibronectins; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin