Lymphatic exosomes promote dendritic cell migration along guidance cues

被引:66
作者
Brown, Markus [1 ,2 ]
Johnson, Louise A. [3 ]
Leone, Dario A. [1 ]
Majek, Peter [4 ]
Vaahtomeri, Kari [2 ,8 ,9 ]
Senfter, Daniel [5 ]
Bukosza, Nora [1 ]
Schachner, Helga [1 ]
Asfour, Gabriele [1 ]
Langer, Brigitte [1 ]
Hauschild, Robert [2 ]
Parapatics, Katja [4 ]
Hong, Young-Kwon [6 ]
Bennett, Keiryn L. [4 ]
Kain, Renate [1 ]
Detmar, Michael [7 ]
Sixt, Michael [2 ]
Jackson, David G. [3 ]
Kerjaschki, Dontscho [1 ]
机构
[1] Med Univ Vienna, Dept Clin Pathol, Vienna, Austria
[2] IST Austria, Klosterneuburg, Austria
[3] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Med Res Council,Human Immunol Unit, Oxford, England
[4] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria
[5] Med Univ Vienna, Dept Pediat & Adolescent Med, Vienna, Austria
[6] Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA
[7] Swiss Fed Inst Technol, Swiss Fed Inst Technol, Inst Pharmaceut Sci, Zurich, Switzerland
[8] Univ Helsinki, Biomedicum Helsinki, Wihuri Res Inst, Helsinki, Finland
[9] Univ Helsinki, Biomedicum Helsinki, Translat Canc Biol Program, Helsinki, Finland
基金
欧洲研究理事会; 英国医学研究理事会; 芬兰科学院; 奥地利科学基金会;
关键词
CHEMOKINE RECEPTOR CX3CR1; EXTRACELLULAR VESICLES; ENDOTHELIAL-CELLS; SAMPLE PREPARATION; IN-VITRO; BREAST-CANCER; EXPRESSION; TRANSMIGRATION; VESSELS; CCL21;
D O I
10.1083/jcb.201612051
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified >1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments.
引用
收藏
页码:2205 / 2221
页数:17
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