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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 the draining lymph node.(a) Schematic of node procession post excision from mouse (b) Dominant node retains a larger quantity of exosomes at 2 hours (c) Dominant node retains a larger quantity of exosomes at 2 days, (d) Quantitation of exosome retention by the dominant and non-dominant nodes at 2 hours and 2 days respectively, (e) Exosome localization within the node at 2 days; (f) Merged image with whole node nuclear staining and exosome localization, (g) magnified area in the node showing exosome localization. Scale bar; 10 um.
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f6: Characterization of exosome retention in the draining lymph node.(a) Schematic of node procession post excision from mouse (b) Dominant node retains a larger quantity of exosomes at 2 hours (c) Dominant node retains a larger quantity of exosomes at 2 days, (d) Quantitation of exosome retention by the dominant and non-dominant nodes at 2 hours and 2 days respectively, (e) Exosome localization within the node at 2 days; (f) Merged image with whole node nuclear staining and exosome localization, (g) magnified area in the node showing exosome localization. Scale bar; 10 um.

Mentions: To investigate the cell populations that were responsible for uptake and retention of the exosomes in the draining lymph nodes, the dominant and non-dominant nodes were analyzed either by immunostaining or digesting the nodes and quantifying co-localization of the exosome signal with immune cells markers using FACS (Fig. 6a). The dominant lymph node contained a significantly higher proportion of exosomes than the non-dominant node, (p-value <0.05) a phenomenon that was observed at both 2 hours and 2 days (Fig. 6b,c respectively). Although the amount of exosomes retained in the cells from the digested node slightly decreased from 2 hours to 2 days post injection in both the dominant and non-dominant nodes, they still contained 10–15% of the injected exosomes and contained 1500-fold higher concentration of exosomes than the axillary lymph node which served as a control for the study as it did not directly drain the site of local exosome injection (Figs 5g and 6d). Within the draining lymph node, exosomes were predominantly present in 2 specific areas: the entire periphery of the node and in small circular areas near the periphery that corresponded to the subscapular sinus (SCS) and the follicular regions of the lymph node respectively (Fig. 6e–g).


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 the draining lymph node.(a) Schematic of node procession post excision from mouse (b) Dominant node retains a larger quantity of exosomes at 2 hours (c) Dominant node retains a larger quantity of exosomes at 2 days, (d) Quantitation of exosome retention by the dominant and non-dominant nodes at 2 hours and 2 days respectively, (e) Exosome localization within the node at 2 days; (f) Merged image with whole node nuclear staining and exosome localization, (g) magnified area in the node showing exosome localization. Scale bar; 10 um.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Characterization of exosome retention in the draining lymph node.(a) Schematic of node procession post excision from mouse (b) Dominant node retains a larger quantity of exosomes at 2 hours (c) Dominant node retains a larger quantity of exosomes at 2 days, (d) Quantitation of exosome retention by the dominant and non-dominant nodes at 2 hours and 2 days respectively, (e) Exosome localization within the node at 2 days; (f) Merged image with whole node nuclear staining and exosome localization, (g) magnified area in the node showing exosome localization. Scale bar; 10 um.
Mentions: To investigate the cell populations that were responsible for uptake and retention of the exosomes in the draining lymph nodes, the dominant and non-dominant nodes were analyzed either by immunostaining or digesting the nodes and quantifying co-localization of the exosome signal with immune cells markers using FACS (Fig. 6a). The dominant lymph node contained a significantly higher proportion of exosomes than the non-dominant node, (p-value <0.05) a phenomenon that was observed at both 2 hours and 2 days (Fig. 6b,c respectively). Although the amount of exosomes retained in the cells from the digested node slightly decreased from 2 hours to 2 days post injection in both the dominant and non-dominant nodes, they still contained 10–15% of the injected exosomes and contained 1500-fold higher concentration of exosomes than the axillary lymph node which served as a control for the study as it did not directly drain the site of local exosome injection (Figs 5g and 6d). Within the draining lymph node, exosomes were predominantly present in 2 specific areas: the entire periphery of the node and in small circular areas near the periphery that corresponded to the subscapular sinus (SCS) and the follicular regions of the lymph node respectively (Fig. 6e–g).

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.