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Published on: January 7, 2019
Different role of CD73 in leukocyte trafficking via blood and lymph vessels
Annika Ålgars1, Marika Karikoski, Gennady G Yegutkin
1MediCity Research Laboratory, University of Turku, Turku, Finland.
Insights
CD73 on lymphocytes, not lymphatic vessels, is crucial for immune cell migration to lymph nodes. This finding clarifies CD73
Area of Science:
- Immunology
- Cell Biology
- Physiology
Background:
- CD73 (ecto-5'-nucleotidase) regulates extracellular ATP metabolism, influencing blood vessel permeability and leukocyte traffic.
- The distribution and function of CD73 on lymphatic vessels remain largely uncharacterized.
- Lymphatic endothelium exhibits distinct extracellular nucleotide metabolism compared to blood vascular endothelium.
Purpose of the Study:
- To investigate the expression and function of CD73 on lymphatic vessels.
- To determine the role of CD73 in lymphocyte trafficking through lymphatic systems.
- To differentiate the roles of endothelial CD73 versus lymphocyte CD73 in immune cell migration.
Main Methods:
- Immunohistochemical analysis of CD73 expression on afferent and efferent lymphatic vessels.
- Comparison of ectonucleotidase activity between lymphatic and blood vascular endothelium.
- Assessment of lymphocyte migration in CD73 knockout mice using lymphatic vessels.
Main Results:
- CD73 is expressed on a subpopulation of afferent lymphatic vessels but absent on efferent lymphatics.
- Lymphatic endothelium shows higher ecto-5'-nucleotidase/CD73 activity than blood vascular endothelium.
- CD73 deficiency in lymphocytes significantly reduces migration to draining lymph nodes (>50%), while CD73-deficient lymphatics maintain efficient trafficking.
Conclusions:
- Endothelial CD73 is not essential for lymphocyte trafficking or permeability in lymphatic vessels.
- Lymphocyte-expressed CD73 plays a critical role in lymphocyte migration via afferent lymphatic vessels.
- These findings highlight distinct roles for CD73 in blood versus lymphatic vascular systems.
Abstract:
CD73 is involved in the extracellular ATP metabolism by dephosphorylating extracellular AMP to adenosine and thus regulating permeability of the blood vessels and leukocyte traffic into the tissues. It is also present on lymphatic vessels where its distribution and function have not been characterized. We found that CD73 is expressed on a subpopulation of afferent lymph vessels but is absent on efferent lymphatics, unlike LYVE-1 and podoplanin, which are expressed on both types of lymphatics. The extracellular nucleotide metabolism on lymphatic endothelium differs from that on blood vessel endothelium as lymphatic endothelium has lower NTPDase and higher ecto-5'-nucleotidase/CD73 activity than blood vascular endothelium. In knockout mice, the lack of CD73 on lymphocytes decreases migration of lymphocytes to the draining lymph nodes more than 50% while CD73-deficient lymph vessels mediate lymphocyte trafficking as efficiently as the wild-type lymphatics. Thus, although endothelial CD73 is important for permeability and leukocyte extravasation in blood vessels, it does not have a role in these functions on lymphatics. Instead, lymphocyte CD73 is intimately involved in lymphocyte migration via afferent lymphatic vessels.
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