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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1463.)
© 2007 American Heart Association, Inc.

Thrombosis

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

Harald F. Langer; Karin Daub; Gregor Braun; Tanja Schönberger; Andreas E. May; Martin Schaller; Gerburg M. Stein; Konstantinos Stellos; Andreas Bueltmann; Dorothea Siegel-Axel; Hans P. Wendel; Hermann Aebert; Martin Roecken; Peter Seizer; Sentot Santoso; Sebastian Wesselborg; Peter Brossart; Meinrad Gawaz

From Innere Medizin (H.F.L., K.D., G.B., T.S., A.E.M., K.S., A.B., D.S.-A., P.S., M.G.), Abteilung III, Eberhard Karls University Tuebingen, Germany; Department of Dermatology (M.S., M.R.), Eberhard Karls University Tuebingen, Germany; Internal Medicine I (G.M.S., S.W.), Eberhard Karls University Tuebingen, Germany; Department of Thoracic, Cardiac, and Vascular Surgery (H.P.W., H.A.), Eberhard Karls University Tuebingen, Germany; Institute for Clinical Immunology and Transfusion Medicine (S.S.), Justus-Liebig-University Giessen; Internal Medicine II (P.B.), Eberhard Karls University Tuebingen, Germany.

Correspondence to Harald F. Langer, MD, Medizinische Klinik III, Eberhard Karls Universität Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany. E-mail harald.langer{at}med.uni-tuebingen.de; or to Meinrad Gawaz, MD, Medizinische Klinik III, Universitätsklinikum Tübingen, Otfried-Müllerstr.10, 72076 Tübingen, Germany. E-mail meinrad.gawaz@med.uni-tuebingen.de

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 _Mβ₂ (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.

Thrombotic events and immunoinflammatory processes take place next to each other in atherosclerotic lesion formation. We show that recruitment of dendritic cells is mediated by platelets in vitro and in vivo and lead to DC activation and apoptosis. This process may be of importance for atherosclerotic lesion progression.

Key Words: adhesion molecules • cell trafficking • dendritic cells • platelets

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