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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 exosomes transport in vivo.(a) Steady state fluorescence in the lymphatic collecting vessel (b) Intensity profile of a specified region of interest of exosome transport in a representative vessel over a 10 minute period, (c) Steady state fluorescence in the draining lymph node, (d) Intensity profile of a specified region of interest of exosome transport in a representative lymph node over a 10 minute period, (e) Arrival time of detectable levels of fluorescence for dominant and non-dominant collecting vessels and draining lymph nodes.
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f4: Characterization of exosomes transport in vivo.(a) Steady state fluorescence in the lymphatic collecting vessel (b) Intensity profile of a specified region of interest of exosome transport in a representative vessel over a 10 minute period, (c) Steady state fluorescence in the draining lymph node, (d) Intensity profile of a specified region of interest of exosome transport in a representative lymph node over a 10 minute period, (e) Arrival time of detectable levels of fluorescence for dominant and non-dominant collecting vessels and draining lymph nodes.

Mentions: The fluorescence arrival in the dominant and non-dominant collecting vessels were analyzed and quantified from the time of injecting the exosome bolus until steady state fluorescence was achieved. The dominant vessel always had significantly higher fluorescence in all trials as compared to the non- dominant vessel (Fig. 4a; p- value <0.05) and representative line intensity profiles are shown for both vessels (Fig. 4b). The fluorescence arrival in the draining lymph nodes were analyzed and similarly, the dominant node (drained by the dominant collecting vessel) was visualized first and was brighter than the non-dominant node, which was visualized later and was fainter (Fig. 4c). Representative line intensity profiles are shown for both the draining lymph nodes (Fig. 4d). There are two distinct regions in the line intensity graphs that corresponding to a) “arrival” where there is a rapid increase in exosome transport and b) “steady state” where the exosomal transport is stable. The packet frequency in the dominant vessel was significantly higher (p-value < 0.05) at arrival as compared to the steady state while the difference in non-dominant packet frequency was not significant (Supp. Fig. 3a, p-value = 0.068). The packet frequency in the lymph nodes followed a similar pattern with a significantly higher frequency in the dominant node as compared to the non-dominant node at both the arrival and steady states (p-value <0.05, Supp. Fig. 3b). The transport times of the dominant vessel was significantly lower with fluorescence first appearing in the dominant vessel at least 30 seconds ahead of the non-dominant vessels [p-value <0.05], and this trend was replicated in the lymph nodes with fluorescence in the dominant node appearing about a 1.5 min before the non-dominant node (Fig. 4e).


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 exosomes transport in vivo.(a) Steady state fluorescence in the lymphatic collecting vessel (b) Intensity profile of a specified region of interest of exosome transport in a representative vessel over a 10 minute period, (c) Steady state fluorescence in the draining lymph node, (d) Intensity profile of a specified region of interest of exosome transport in a representative lymph node over a 10 minute period, (e) Arrival time of detectable levels of fluorescence for dominant and non-dominant collecting vessels and draining lymph nodes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Characterization of exosomes transport in vivo.(a) Steady state fluorescence in the lymphatic collecting vessel (b) Intensity profile of a specified region of interest of exosome transport in a representative vessel over a 10 minute period, (c) Steady state fluorescence in the draining lymph node, (d) Intensity profile of a specified region of interest of exosome transport in a representative lymph node over a 10 minute period, (e) Arrival time of detectable levels of fluorescence for dominant and non-dominant collecting vessels and draining lymph nodes.
Mentions: The fluorescence arrival in the dominant and non-dominant collecting vessels were analyzed and quantified from the time of injecting the exosome bolus until steady state fluorescence was achieved. The dominant vessel always had significantly higher fluorescence in all trials as compared to the non- dominant vessel (Fig. 4a; p- value <0.05) and representative line intensity profiles are shown for both vessels (Fig. 4b). The fluorescence arrival in the draining lymph nodes were analyzed and similarly, the dominant node (drained by the dominant collecting vessel) was visualized first and was brighter than the non-dominant node, which was visualized later and was fainter (Fig. 4c). Representative line intensity profiles are shown for both the draining lymph nodes (Fig. 4d). There are two distinct regions in the line intensity graphs that corresponding to a) “arrival” where there is a rapid increase in exosome transport and b) “steady state” where the exosomal transport is stable. The packet frequency in the dominant vessel was significantly higher (p-value < 0.05) at arrival as compared to the steady state while the difference in non-dominant packet frequency was not significant (Supp. Fig. 3a, p-value = 0.068). The packet frequency in the lymph nodes followed a similar pattern with a significantly higher frequency in the dominant node as compared to the non-dominant node at both the arrival and steady states (p-value <0.05, Supp. Fig. 3b). The transport times of the dominant vessel was significantly lower with fluorescence first appearing in the dominant vessel at least 30 seconds ahead of the non-dominant vessels [p-value <0.05], and this trend was replicated in the lymph nodes with fluorescence in the dominant node appearing about a 1.5 min before the non-dominant node (Fig. 4e).

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.