Platelets Recruit Human Dendritic Cells Via Mac-1/JAM-C Interaction and Modulate Dendritic Cell Function In Vitro

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 27; no. 6; pp. 1463 - 1470
• Main Authors: Langer, Harald F., Daub, Karin, Braun, Gregor, Schönberger, Tanja, May, Andreas E., Schaller, Martin, Stein, Gerburg M., Stellos, Konstantinos, Bueltmann, Andreas, Siegel-Axel, Dorothea, Wendel, Hans P., Aebert, Hermann, Roecken, Martin, Seizer, Peter, Santoso, Sentot, Wesselborg, Sebastian, Brossart, Peter, Gawaz, Meinrad
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.06.2007; Hagerstown, MD Lippincott
• Subjects: Animals; Apoptosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; Blood Platelets - metabolism; Blood vessels and receptors; Cardiology. Vascular system; Carotid Artery Diseases - blood; Carotid Artery Diseases - metabolism; Carotid Artery Diseases - physiopathology; Carotid Artery, Common - surgery; CD36 Antigens - metabolism; Cell Adhesion; Cell Adhesion Molecules - metabolism; Cell Communication; Cell Differentiation; Cell Movement; Cells, Cultured; Dendritic Cells - metabolism; Dendritic Cells - pathology; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fundamental and applied biological sciences. Psychology; Humans; Lymphocyte Activation; Lymphocytes - metabolism; Macrophage-1 Antigen - metabolism; Medical sciences; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Phagocytosis; Platelet; Signal Transduction; Time Factors; Vertebrates: cardiovascular system; Vascular disease; Human; Dendritic cell; Platelet; dendritic cells; adhesion molecules; Atherosclerosis; Cardiovascular disease; cell trafficking; platelets
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.107.141515

OBJECTIVE—Thrombotic events and immunoinflammatory processes take place next to each other during vascular remodeling in atherosclerotic lesions. In this study we investigated the interaction of platelets with dendritic cells (DCs). METHODS AND RESULTS—The rolling of DCs on platelets was mediated by PSGL-1. Firm adhesion of DCs was mediated through integrin αMβ2 (Mac-1). In vivo, adhesion of DCs to injured carotid arteries in mice was mediated by platelets. Pretreatment with soluble GPVI, which inhibits platelet adhesion to collagen, substantially reduced recruitment of DCs to the injured vessel wall. In addition, preincubation of DCs with sJAM-C significantly reduced their adhesion to platelets. Coincubation of DCs with platelets induced maturation of DCs, as shown by enhanced expression of CD83. In the presence of platelets, DC-induced lymphocyte proliferation was significantly enhanced. Moreover, coincubation of DCs with platelets resulted in platelet phagocytosis by DCs, as verified by different cell phagocytosis assays. Finally, platelet/DC interaction resulted in apoptosis of DCs mediated by a JAM-C–dependent mechanism. CONCLUSIONS—Recruitment of DCs by platelets, which is mediated via CD11b/CD18 (Mac-1) and platelet JAM-C, leads to DC activation and platelet phagocytosis. This process may be of importance for progression of atherosclerotic lesions.