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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.


Characterization of exosome retention in vivo.Exosomes are detected in the node rapidly: (a) Only the dominant node is visible at 5 mins in vivo, (b) Both nodes are visible at 15 mins in vivo, (c) Draining lymph nodes visualized at 2 h pre-excision (in animal), (d) Excised lymph nodes at 2 h post injection, (e) Draining lymph nodes visualized at 2d pre-excision (in animal) (f) Excised lymph nodes at 2 days post injection, Scale = 5 mm. (g) Biodistribution of exosomes in mice organs analyzed at 2 hours and 2 days post injection and (h) quantitation of exosomes and beads retained in the lymph node 1 hour post injection as determined by fluorescence.
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f5: Characterization of exosome retention in vivo.Exosomes are detected in the node rapidly: (a) Only the dominant node is visible at 5 mins in vivo, (b) Both nodes are visible at 15 mins in vivo, (c) Draining lymph nodes visualized at 2 h pre-excision (in animal), (d) Excised lymph nodes at 2 h post injection, (e) Draining lymph nodes visualized at 2d pre-excision (in animal) (f) Excised lymph nodes at 2 days post injection, Scale = 5 mm. (g) Biodistribution of exosomes in mice organs analyzed at 2 hours and 2 days post injection and (h) quantitation of exosomes and beads retained in the lymph node 1 hour post injection as determined by fluorescence.

Mentions: The exosome bolus was rapidly seen in the sciatic lymph nodes drained by the collecting lymphatics with the fluorescence arriving in both the dominant (Fig. 5a) and non-dominant node within 5 min (Fig. 5b, Supp. Video 2). The nodes reached a steady state of fluorescence much like the collecting vessels by 30 min post injection; however unlike the vessels where the fluorescence disappeared within 24 hours, the lymph node fluorescence was detectable through the skin for at least 2 days after injection (Fig. 5c,e respectively). The nodes upon excision at 2 hours and 2 days were strongly fluorescent (Fig. 5d,f respectively).


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

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

Characterization of exosome retention in vivo.Exosomes are detected in the node rapidly: (a) Only the dominant node is visible at 5 mins in vivo, (b) Both nodes are visible at 15 mins in vivo, (c) Draining lymph nodes visualized at 2 h pre-excision (in animal), (d) Excised lymph nodes at 2 h post injection, (e) Draining lymph nodes visualized at 2d pre-excision (in animal) (f) Excised lymph nodes at 2 days post injection, Scale = 5 mm. (g) Biodistribution of exosomes in mice organs analyzed at 2 hours and 2 days post injection and (h) quantitation of exosomes and beads retained in the lymph node 1 hour post injection as determined by fluorescence.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Characterization of exosome retention in vivo.Exosomes are detected in the node rapidly: (a) Only the dominant node is visible at 5 mins in vivo, (b) Both nodes are visible at 15 mins in vivo, (c) Draining lymph nodes visualized at 2 h pre-excision (in animal), (d) Excised lymph nodes at 2 h post injection, (e) Draining lymph nodes visualized at 2d pre-excision (in animal) (f) Excised lymph nodes at 2 days post injection, Scale = 5 mm. (g) Biodistribution of exosomes in mice organs analyzed at 2 hours and 2 days post injection and (h) quantitation of exosomes and beads retained in the lymph node 1 hour post injection as determined by fluorescence.
Mentions: The exosome bolus was rapidly seen in the sciatic lymph nodes drained by the collecting lymphatics with the fluorescence arriving in both the dominant (Fig. 5a) and non-dominant node within 5 min (Fig. 5b, Supp. Video 2). The nodes reached a steady state of fluorescence much like the collecting vessels by 30 min post injection; however unlike the vessels where the fluorescence disappeared within 24 hours, the lymph node fluorescence was detectable through the skin for at least 2 days after injection (Fig. 5c,e respectively). The nodes upon excision at 2 hours and 2 days were strongly fluorescent (Fig. 5d,f respectively).

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.