Ecto‐5′‐nucleotidase/CD73 enhances endothelial barrier function and sprouting in blood but not lymphatic vasculature |
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| Authors: | Gennady G. Yegutkin Kaisa Auvinen Pia Rantakari Maija Hollmén Marika Karikoski Reidar Grénman Kati Elima Sirpa Jalkanen Marko Salmi |
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| Affiliation: | 1. Medicity Research Laboratory, University of Turku, Turku, Finland;2. Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland;3. Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland;4. Department of Otorhinolaryngology—Head and Neck Surgery, Turku University Hospital, Turku, Finland;5. Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland |
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| Abstract: | CD73/ecto‐5′‐nucleotidase is a key enzyme in the regulation of purinergic signaling and inflammatory reactions. It hydrolyzes extracellular AMP into adenosine, which dampens immune cell activation, and reduces leukocyte trafficking. By comparing CD73 expression and function in mononuclear and endothelial cells (ECs) of blood and lymph, we show that extracellular purines and CD73 activity have differential effects in these two vascular systems. We found that CD8‐positive T lymphocytes and CD19‐positive B lymphocytes in human lymph expressed high levels of CD73 and other purinergic enzymes and adenosine receptors. Soluble CD73 was less abundant in human lymph than in serum, whereas CD73 activity was higher in afferent lymphatic ECs than in blood ECs. Adenosine signaling improved barrier function and induced sprouting of human blood, but not lymphatic, ECs in vitro. Similarly, using CD73‐deficient mice we found that CD73 controls only blood vascular permeability at selected lymphoid organs under physiological conditions. Thus, both vascular and lymphatic arms of the immune system synthesize the components of purinergic signaling system, but surprisingly they use CD73 differentially to control endothelial permeability and sprouting. |
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| Keywords: | adenosine endothelial cells lymphatics permeability purinergic signaling |
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