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Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

Srinivasan S, Vannberg FO, Dixon JB - Sci Rep (2016)

Bottom Line: Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow.Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake.Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

View Article: PubMed Central - PubMed

Affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.

ABSTRACT
It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

No MeSH data available.


Localization of exosomes within the lymph node.Shown are serial lymph node sections at 2 days following injection of 10 ug of exosomes (green). Immune cells were identified as indicated (red) with antibodies against (a) CD11b (macrophages), (b) CD169 (macrophages), and (c) CD19 (B-cells), (d) CD81(red) was used as a secondary localization marker to confirm exosome retention in the node. White scale bar = 50 um while yellow scale bar is 5 um.
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f8: Localization of exosomes within the lymph node.Shown are serial lymph node sections at 2 days following injection of 10 ug of exosomes (green). Immune cells were identified as indicated (red) with antibodies against (a) CD11b (macrophages), (b) CD169 (macrophages), and (c) CD19 (B-cells), (d) CD81(red) was used as a secondary localization marker to confirm exosome retention in the node. White scale bar = 50 um while yellow scale bar is 5 um.

Mentions: Finally, we confirmed the co-localization of exosomes with CD11b macrophages and CD19 B-cells by immunostaining frozen lymph node sections. We observed a strong co-occurrence of PKH (green) signal from the exosomes with CD11b from the macrophages and CD19 from the B-cells (Fig. 8a,c respectively). Additionally, we also checked for CD169 co-localization with exosomes to confirm macrophage mediated exosome capture (Fig. 8b). In order to ensure that the PKH signal is still present on intact exosomes, we checked for CD81 expression and found a very high degree of CD81 and PKH co-occurrence indicating that the dye was still associated with the exosomal membrane (Fig. 8d).


Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

Srinivasan S, Vannberg FO, Dixon JB - Sci Rep (2016)

Localization of exosomes within the lymph node.Shown are serial lymph node sections at 2 days following injection of 10 ug of exosomes (green). Immune cells were identified as indicated (red) with antibodies against (a) CD11b (macrophages), (b) CD169 (macrophages), and (c) CD19 (B-cells), (d) CD81(red) was used as a secondary localization marker to confirm exosome retention in the node. White scale bar = 50 um while yellow scale bar is 5 um.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834495&req=5

f8: Localization of exosomes within the lymph node.Shown are serial lymph node sections at 2 days following injection of 10 ug of exosomes (green). Immune cells were identified as indicated (red) with antibodies against (a) CD11b (macrophages), (b) CD169 (macrophages), and (c) CD19 (B-cells), (d) CD81(red) was used as a secondary localization marker to confirm exosome retention in the node. White scale bar = 50 um while yellow scale bar is 5 um.
Mentions: Finally, we confirmed the co-localization of exosomes with CD11b macrophages and CD19 B-cells by immunostaining frozen lymph node sections. We observed a strong co-occurrence of PKH (green) signal from the exosomes with CD11b from the macrophages and CD19 from the B-cells (Fig. 8a,c respectively). Additionally, we also checked for CD169 co-localization with exosomes to confirm macrophage mediated exosome capture (Fig. 8b). In order to ensure that the PKH signal is still present on intact exosomes, we checked for CD81 expression and found a very high degree of CD81 and PKH co-occurrence indicating that the dye was still associated with the exosomal membrane (Fig. 8d).

Bottom Line: Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow.Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake.Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

View Article: PubMed Central - PubMed

Affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.

ABSTRACT
It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

No MeSH data available.