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The Ecto-5’-Nucleotidase/CD73 Inhibitor, α,β-Methylene Adenosine 5’-Diphosphate, Exacerbates Carrageenan-Induced Pleurisy in Rat

The ecto-5’-nucleotidase (ecto-5’NT/CD73) represents a crucial enzyme for endogenous adenosine generation. Several findings have shown that CD73 plays an important role in regulating vascular permeability and immune cell function. Adenosine 5’-(α,β-methylene)diphosphate (APCP) is a CD73 inhibitor, w...

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Autores principales: Caiazzo, Elisabetta, Morello, Silvana, Carnuccio, Rosa, Ialenti, Armando, Cicala, Carla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637294/
https://www.ncbi.nlm.nih.gov/pubmed/31354490
http://dx.doi.org/10.3389/fphar.2019.00775
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author Caiazzo, Elisabetta
Morello, Silvana
Carnuccio, Rosa
Ialenti, Armando
Cicala, Carla
author_facet Caiazzo, Elisabetta
Morello, Silvana
Carnuccio, Rosa
Ialenti, Armando
Cicala, Carla
author_sort Caiazzo, Elisabetta
collection PubMed
description The ecto-5’-nucleotidase (ecto-5’NT/CD73) represents a crucial enzyme for endogenous adenosine generation. Several findings have shown that CD73 plays an important role in regulating vascular permeability and immune cell function. Adenosine 5’-(α,β-methylene)diphosphate (APCP) is a CD73 inhibitor, widely used as pharmacological tool to investigate the role of CD73/adenosine pathway in several in vitro and in vivo models, although it has been also shown to inhibit other ectoenzymes involved in adenosinergic pathway. Here, we evaluated the effect of APCP in the development of inflammation in carrageenan-induced pleurisy model. We found that treatment with APCP (400 µg/rat) significantly increased cell accumulation, exudate formation, and pro-inflammatory cytokine content into the pleural cavity in the acute phase (4 h) of inflammation, with no differences in the sub-acute phase (72 h) except for the regulation of monocyte chemotactic protein-1 levels. In addition, cells collected by pleural lavage fluids of APCP-treated rats, 4 h following carrageenan injection, showed increased ability to migrate in vitro, both in presence and in absence of N-formyl-L-methionyl-L-leucyl-L-phenylalanine as chemotactic stimulus, compared to cells obtained by control rats. Our results demonstrate that APCP exacerbates the early phase of carrageenan-induced pleurisy by controlling pleural effusion and polymorphonuclear migration in vivo and ex vivo. This effect is likely dependent upon CD73 inhibition, although an inhibitory effect of other ectoenzymes cannot be ruled out.
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spelling pubmed-66372942019-07-26 The Ecto-5’-Nucleotidase/CD73 Inhibitor, α,β-Methylene Adenosine 5’-Diphosphate, Exacerbates Carrageenan-Induced Pleurisy in Rat Caiazzo, Elisabetta Morello, Silvana Carnuccio, Rosa Ialenti, Armando Cicala, Carla Front Pharmacol Pharmacology The ecto-5’-nucleotidase (ecto-5’NT/CD73) represents a crucial enzyme for endogenous adenosine generation. Several findings have shown that CD73 plays an important role in regulating vascular permeability and immune cell function. Adenosine 5’-(α,β-methylene)diphosphate (APCP) is a CD73 inhibitor, widely used as pharmacological tool to investigate the role of CD73/adenosine pathway in several in vitro and in vivo models, although it has been also shown to inhibit other ectoenzymes involved in adenosinergic pathway. Here, we evaluated the effect of APCP in the development of inflammation in carrageenan-induced pleurisy model. We found that treatment with APCP (400 µg/rat) significantly increased cell accumulation, exudate formation, and pro-inflammatory cytokine content into the pleural cavity in the acute phase (4 h) of inflammation, with no differences in the sub-acute phase (72 h) except for the regulation of monocyte chemotactic protein-1 levels. In addition, cells collected by pleural lavage fluids of APCP-treated rats, 4 h following carrageenan injection, showed increased ability to migrate in vitro, both in presence and in absence of N-formyl-L-methionyl-L-leucyl-L-phenylalanine as chemotactic stimulus, compared to cells obtained by control rats. Our results demonstrate that APCP exacerbates the early phase of carrageenan-induced pleurisy by controlling pleural effusion and polymorphonuclear migration in vivo and ex vivo. This effect is likely dependent upon CD73 inhibition, although an inhibitory effect of other ectoenzymes cannot be ruled out. Frontiers Media S.A. 2019-07-11 /pmc/articles/PMC6637294/ /pubmed/31354490 http://dx.doi.org/10.3389/fphar.2019.00775 Text en Copyright © 2019 Caiazzo, Morello, Carnuccio, Ialenti and Cicala http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Caiazzo, Elisabetta
Morello, Silvana
Carnuccio, Rosa
Ialenti, Armando
Cicala, Carla
The Ecto-5’-Nucleotidase/CD73 Inhibitor, α,β-Methylene Adenosine 5’-Diphosphate, Exacerbates Carrageenan-Induced Pleurisy in Rat
title The Ecto-5’-Nucleotidase/CD73 Inhibitor, α,β-Methylene Adenosine 5’-Diphosphate, Exacerbates Carrageenan-Induced Pleurisy in Rat
title_full The Ecto-5’-Nucleotidase/CD73 Inhibitor, α,β-Methylene Adenosine 5’-Diphosphate, Exacerbates Carrageenan-Induced Pleurisy in Rat
title_fullStr The Ecto-5’-Nucleotidase/CD73 Inhibitor, α,β-Methylene Adenosine 5’-Diphosphate, Exacerbates Carrageenan-Induced Pleurisy in Rat
title_full_unstemmed The Ecto-5’-Nucleotidase/CD73 Inhibitor, α,β-Methylene Adenosine 5’-Diphosphate, Exacerbates Carrageenan-Induced Pleurisy in Rat
title_short The Ecto-5’-Nucleotidase/CD73 Inhibitor, α,β-Methylene Adenosine 5’-Diphosphate, Exacerbates Carrageenan-Induced Pleurisy in Rat
title_sort ecto-5’-nucleotidase/cd73 inhibitor, α,β-methylene adenosine 5’-diphosphate, exacerbates carrageenan-induced pleurisy in rat
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637294/
https://www.ncbi.nlm.nih.gov/pubmed/31354490
http://dx.doi.org/10.3389/fphar.2019.00775
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