Mast cell-derived particles deliver peripheral signals to remote lymph nodes.
During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.
Kunder
Christian A
CA
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
St John
Ashley L
AL
Li
Guojie
G
Leong
Kam W
KW
Berwin
Brent
B
Staats
Herman F
HF
Abraham
Soman N
SN
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000378:metabolism; D048271:Chitosan / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D042601:Lymphatic Vessels / Q000187:drug effects / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D012995:Solubility / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018836:Inflammation Mediators; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin; D048271:Chitosan; D013755:Tetradecanoylphorbol Acetate