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Review
. 2021 May 1;206(9):1983-1990.
doi: 10.4049/jimmunol.2001342.

Ectonucleotidases in Inflammation, Immunity, and Cancer

Clarissa Branco Haas  1 , Marianna Lovászi  1 , Elizandra Braganhol  2 , Pál Pacher  3 , György Haskó  4
Affiliations
Review

Ectonucleotidases in Inflammation, Immunity, and Cancer

Clarissa Branco Haas et al. J Immunol. .

Abstract

Nucleoside triphosphate diphosphohydrolases (NTPDases) are a family of enzymes that hydrolyze nucleotides such as ATP, UTP, ADP, and UDP to monophosphates derivates such as AMP and UMP. The NTPDase family consists of eight enzymes, of which NTPDases 1, 2, 3, and 8 are expressed on cell membranes thereby hydrolyzing extracellular nucleotides. Cell membrane NTPDases are expressed in all tissues, in which they regulate essential physiological tissue functions such as development, blood flow, hormone secretion, and neurotransmitter release. They do so by modulating nucleotide-mediated purinergic signaling through P2 purinergic receptors. NTPDases 1, 2, 3, and 8 also play a key role during infection, inflammation, injury, and cancer. Under these conditions, NTPDases can contribute and control the pathophysiology of infectious, inflammatory diseases and cancer. In this review, we discuss the role of NTPDases, focusing on the less understood NTPDases 2-8, in regulating inflammation and immunity during infectious, inflammatory diseases, and cancer.

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Conflict of interest statement

Conflict of Interest Information

G.H. owns stock in Purine Pharmaceuticals, Inc. The other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Cellular localization and function of E-NTPDase isotypes. NTPDase 1, 2, 3 and 8 are transmembrane enzymes that face the extracellular milieu. NTPDases 4, 5, 6 and 7 are localized in the intracellular milieu. NTPDase 4 is expressed in Lysosomes and Autophagic Vacuole. NTPDase 5 is expressed in Endoplasmic Reticulum (ER). NTPDase 6 is expressed in the Golgi Apparatus and NTPDase 7 is expressed in vesicles. NTPDase: Nucleoside triphosphate diphosphohydrolase; ATP: Adenosine triphosphate; UTP: Uridine triphosphate; ADP: Adenosine diphosphate; UDP: Uridine diphosphate; AMP: Adenosine monophosphate; UMP: Uridine monophosphate. Created with BioRender.com.
Figure 2.
Figure 2.
NTPDases expression and function in innate and adaptative immune cells. NTPDase: Nucleoside triphosphate diphosphohydrolase; ATP: Adenosine triphosphate; NK: Natural killer cells; ILC3: innate lymphoid cells type 3. Created with BioRender.com.
See this image and copyright information in PMC

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