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.
Highlights
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
Exosomes had a spherical shape with a diameter of ~60–75 nm as seen from scanning electron microscopy which agreed with previous reports of exosome shape and size reported in literature[20] (Fig. 1b)
Macrophages can release exosomes that carry specific antigens to initiate an immune response at the node: M. tuberculosis infected macrophages released exosomes containing mycobacterial lipoproteins which were able to stimulate a pro-inflammatory response in mice[6]
Summary
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. 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, priming the node for a more effective immune response. The discovery of functional, transportable mRNA and miRNA within exosomes further increases the complexity of cell-to-cell communication They can fuse with the recipient cells and deliver their contents into the cytoplasm of the recipient cell and perturb the recipient cell, especially since miRNA can mediate RNA interference[4]. Particles smaller than this are taken up in the blood capillaries and larger particles typically become trapped in the extracellular matrix[10,11], more recent evidence suggests that particles as large as 1 micron could be taken up by lymphatics[12]
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