Platelets recruit human dendritic cells via Mac-1/JAM-C interaction and modulate dendritic cell function in vitro.
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).


RESULTS
The rolling of DCs on platelets was mediated by PSGL-1. Firm adhesion of DCs was mediated through integrin alphaMbeta2 (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.
Langer
Harald F
HF
Innere Medizin, Abteilung III, Eberhard Karls Universität Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany. harald.langer@med.uni-tuebingen.de
Daub
Karin
K
Braun
Gregor
G
Schönberger
Tanja
T
May
Andreas E
AE
Schaller
Martin
M
Stein
Gerburg M
GM
Stellos
Konstantinos
K
Bueltmann
Andreas
A
Siegel-Axel
Dorothea
D
Wendel
Hans P
HP
Aebert
Hermann
H
Roecken
Martin
M
Seizer
Peter
P
Santoso
Sentot
S
Wesselborg
Sebastian
S
Brossart
Peter
P
Gawaz
Meinrad
M
D000818:Animals; D017209:Apoptosis; D001792:Blood Platelets / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000601:surgery; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D015398:Signal Transduction; D013997:Time Factors
D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; C448000:JAM3 protein, human; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein