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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.


Related in: MedlinePlus

Exosomes are transported rapidly through the lymphatic endothelium in vivo.(a) Dual labeling of exosomes, (b) injection and visualization scheme in mice. Exosomes are detected in the lymphatics rapidly (c) vessel at 0 mins, (d) vessel at 2 mins, (e) vessel at 5 mins, (f) vessel at 20 mins (g) vessel at 2 hours, (h) vessel at 2 days, (i) lymphatic capillaries seen close to the injection site at 2 hours, (j) injection site at 2 hours, and (k) injection site at 2 days. Scale bar; 5 mm.
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f3: Exosomes are transported rapidly through the lymphatic endothelium in vivo.(a) Dual labeling of exosomes, (b) injection and visualization scheme in mice. Exosomes are detected in the lymphatics rapidly (c) vessel at 0 mins, (d) vessel at 2 mins, (e) vessel at 5 mins, (f) vessel at 20 mins (g) vessel at 2 hours, (h) vessel at 2 days, (i) lymphatic capillaries seen close to the injection site at 2 hours, (j) injection site at 2 hours, and (k) injection site at 2 days. Scale bar; 5 mm.

Mentions: To track the movement of exosomes real time in vivo, a near-infrared fluorophore was conjugated to the N-terminal of exosomal membrane proteins. A second fluorophore was added in the lipid bilayer of the exosomes to enable ex-vivo, multi scale analysis of cellular exosome uptake and transport (Fig. 3a). Mice were injected intradermally with a 10 µg bolus of dual labeled exosomes in 10 µL of PBS. The near-infrared excitation source and the field of view of the CCD emission detector were centered on the mouse tail 10 cm downstream (toward the base of the tail) from the injection site at the tip of tail (Fig. 3b). This location ensured that only the downstream collecting lymphatics would be visualized so as to maximize detection sensitivity and avoid image saturation from the injection site (Fig. 3i).


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

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

Exosomes are transported rapidly through the lymphatic endothelium in vivo.(a) Dual labeling of exosomes, (b) injection and visualization scheme in mice. Exosomes are detected in the lymphatics rapidly (c) vessel at 0 mins, (d) vessel at 2 mins, (e) vessel at 5 mins, (f) vessel at 20 mins (g) vessel at 2 hours, (h) vessel at 2 days, (i) lymphatic capillaries seen close to the injection site at 2 hours, (j) injection site at 2 hours, and (k) injection site at 2 days. Scale bar; 5 mm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Exosomes are transported rapidly through the lymphatic endothelium in vivo.(a) Dual labeling of exosomes, (b) injection and visualization scheme in mice. Exosomes are detected in the lymphatics rapidly (c) vessel at 0 mins, (d) vessel at 2 mins, (e) vessel at 5 mins, (f) vessel at 20 mins (g) vessel at 2 hours, (h) vessel at 2 days, (i) lymphatic capillaries seen close to the injection site at 2 hours, (j) injection site at 2 hours, and (k) injection site at 2 days. Scale bar; 5 mm.
Mentions: To track the movement of exosomes real time in vivo, a near-infrared fluorophore was conjugated to the N-terminal of exosomal membrane proteins. A second fluorophore was added in the lipid bilayer of the exosomes to enable ex-vivo, multi scale analysis of cellular exosome uptake and transport (Fig. 3a). Mice were injected intradermally with a 10 µg bolus of dual labeled exosomes in 10 µL of PBS. The near-infrared excitation source and the field of view of the CCD emission detector were centered on the mouse tail 10 cm downstream (toward the base of the tail) from the injection site at the tip of tail (Fig. 3b). This location ensured that only the downstream collecting lymphatics would be visualized so as to maximize detection sensitivity and avoid image saturation from the injection site (Fig. 3i).

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.


Related in: MedlinePlus