ATP secreted by endothelial cells blocks CX 3CL1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y 11 receptor activation

Stefania Gorini, Giulia Callegari, Giulia Romagnoli, Caterina Mammi, Domenico Mavilio, Giuseppe Rosano, Massimo Fini, Francesco Di Virgilio, Sara Gulinelli, Simonetta Falzoni, Andrea Cavani, Davide Ferrari, Andrea La Sala

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Endothelial cells (ECs) represent a major source of actively secreted adenosine triphosphate (ATP). Natural killer (NK) cells can mediate vascular injury in several pathologic conditions, including cytomegalovirus infection and vascular leak syndrome. We studied NKcell expression of P2 receptors and the role of these nucleotide receptors in the regulation of endothelial-NK cell crosstalk. NK cells from healthy subjects expressed P2Y 1,2,4,6,11,12,13,14 and P2X 1,4,5,6,7 receptors. NK cells stimulated with ATP, but not uridine triphosphate, increased intracellular Ca 2+ and chemokinesis. Moreover, ATP, but not uridine triphosphate, inhibited NK chemotaxis in response to CX 3CL1, whereas chemotaxis to CXCL12 was increased. CX 3CL1 elicited killing of human umbilical vein ECs and human coronary artery ECs by NK cells. However, in the presence of ATP, CX 3CL1 failed to stimulate killing of ECs. Such inhibitory effect was lost on exogenous addition of the ATP-hydrolyzing enzyme apyrase or by pharmacologic inhibition of the P2Y 11R, and correlated with increased intracellular cyclic adenosine monophosphate concentrations induced by ATP or other P2Y 11R agonists, including NAD +. Extracellular ATP regulates NK-cell cytotoxicity via P2Y 11R activation, protecting ECs from CX 3CL1-elicited NK cell-mediated killing. These findings point out the P2Y 11R as a potential target for pharmacologic intervention aimed at reducing NK-mediated vascular injury.

Original languageEnglish
Pages (from-to)4492-4500
Number of pages9
JournalBlood
Volume116
Issue number22
DOIs
Publication statusPublished - Nov 25 2010

Fingerprint

Endothelial cells
Chemotaxis
Cytotoxicity
Natural Killer Cells
Endothelial Cells
Adenosine Triphosphate
Chemical activation
Uridine Triphosphate
Vascular System Injuries
Apyrase
Human Umbilical Vein Endothelial Cells
Cytomegalovirus Infections
Crosstalk
Cyclic AMP
NAD
Blood Vessels
Coronary Vessels
Healthy Volunteers
Nucleotides
Enzymes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

ATP secreted by endothelial cells blocks CX 3CL1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y 11 receptor activation. / Gorini, Stefania; Callegari, Giulia; Romagnoli, Giulia; Mammi, Caterina; Mavilio, Domenico; Rosano, Giuseppe; Fini, Massimo; Di Virgilio, Francesco; Gulinelli, Sara; Falzoni, Simonetta; Cavani, Andrea; Ferrari, Davide; La Sala, Andrea.

In: Blood, Vol. 116, No. 22, 25.11.2010, p. 4492-4500.

Research output: Contribution to journalArticle

Gorini, Stefania ; Callegari, Giulia ; Romagnoli, Giulia ; Mammi, Caterina ; Mavilio, Domenico ; Rosano, Giuseppe ; Fini, Massimo ; Di Virgilio, Francesco ; Gulinelli, Sara ; Falzoni, Simonetta ; Cavani, Andrea ; Ferrari, Davide ; La Sala, Andrea. / ATP secreted by endothelial cells blocks CX 3CL1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y 11 receptor activation. In: Blood. 2010 ; Vol. 116, No. 22. pp. 4492-4500.
@article{4599e5d72c49478eb640d19b1b101fe8,
title = "ATP secreted by endothelial cells blocks CX 3CL1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y 11 receptor activation",
abstract = "Endothelial cells (ECs) represent a major source of actively secreted adenosine triphosphate (ATP). Natural killer (NK) cells can mediate vascular injury in several pathologic conditions, including cytomegalovirus infection and vascular leak syndrome. We studied NKcell expression of P2 receptors and the role of these nucleotide receptors in the regulation of endothelial-NK cell crosstalk. NK cells from healthy subjects expressed P2Y 1,2,4,6,11,12,13,14 and P2X 1,4,5,6,7 receptors. NK cells stimulated with ATP, but not uridine triphosphate, increased intracellular Ca 2+ and chemokinesis. Moreover, ATP, but not uridine triphosphate, inhibited NK chemotaxis in response to CX 3CL1, whereas chemotaxis to CXCL12 was increased. CX 3CL1 elicited killing of human umbilical vein ECs and human coronary artery ECs by NK cells. However, in the presence of ATP, CX 3CL1 failed to stimulate killing of ECs. Such inhibitory effect was lost on exogenous addition of the ATP-hydrolyzing enzyme apyrase or by pharmacologic inhibition of the P2Y 11R, and correlated with increased intracellular cyclic adenosine monophosphate concentrations induced by ATP or other P2Y 11R agonists, including NAD +. Extracellular ATP regulates NK-cell cytotoxicity via P2Y 11R activation, protecting ECs from CX 3CL1-elicited NK cell-mediated killing. These findings point out the P2Y 11R as a potential target for pharmacologic intervention aimed at reducing NK-mediated vascular injury.",
author = "Stefania Gorini and Giulia Callegari and Giulia Romagnoli and Caterina Mammi and Domenico Mavilio and Giuseppe Rosano and Massimo Fini and {Di Virgilio}, Francesco and Sara Gulinelli and Simonetta Falzoni and Andrea Cavani and Davide Ferrari and {La Sala}, Andrea",
year = "2010",
month = "11",
day = "25",
doi = "10.1182/blood-2009-12-260828",
language = "English",
volume = "116",
pages = "4492--4500",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "22",

}

TY - JOUR

T1 - ATP secreted by endothelial cells blocks CX 3CL1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y 11 receptor activation

AU - Gorini, Stefania

AU - Callegari, Giulia

AU - Romagnoli, Giulia

AU - Mammi, Caterina

AU - Mavilio, Domenico

AU - Rosano, Giuseppe

AU - Fini, Massimo

AU - Di Virgilio, Francesco

AU - Gulinelli, Sara

AU - Falzoni, Simonetta

AU - Cavani, Andrea

AU - Ferrari, Davide

AU - La Sala, Andrea

PY - 2010/11/25

Y1 - 2010/11/25

N2 - Endothelial cells (ECs) represent a major source of actively secreted adenosine triphosphate (ATP). Natural killer (NK) cells can mediate vascular injury in several pathologic conditions, including cytomegalovirus infection and vascular leak syndrome. We studied NKcell expression of P2 receptors and the role of these nucleotide receptors in the regulation of endothelial-NK cell crosstalk. NK cells from healthy subjects expressed P2Y 1,2,4,6,11,12,13,14 and P2X 1,4,5,6,7 receptors. NK cells stimulated with ATP, but not uridine triphosphate, increased intracellular Ca 2+ and chemokinesis. Moreover, ATP, but not uridine triphosphate, inhibited NK chemotaxis in response to CX 3CL1, whereas chemotaxis to CXCL12 was increased. CX 3CL1 elicited killing of human umbilical vein ECs and human coronary artery ECs by NK cells. However, in the presence of ATP, CX 3CL1 failed to stimulate killing of ECs. Such inhibitory effect was lost on exogenous addition of the ATP-hydrolyzing enzyme apyrase or by pharmacologic inhibition of the P2Y 11R, and correlated with increased intracellular cyclic adenosine monophosphate concentrations induced by ATP or other P2Y 11R agonists, including NAD +. Extracellular ATP regulates NK-cell cytotoxicity via P2Y 11R activation, protecting ECs from CX 3CL1-elicited NK cell-mediated killing. These findings point out the P2Y 11R as a potential target for pharmacologic intervention aimed at reducing NK-mediated vascular injury.

AB - Endothelial cells (ECs) represent a major source of actively secreted adenosine triphosphate (ATP). Natural killer (NK) cells can mediate vascular injury in several pathologic conditions, including cytomegalovirus infection and vascular leak syndrome. We studied NKcell expression of P2 receptors and the role of these nucleotide receptors in the regulation of endothelial-NK cell crosstalk. NK cells from healthy subjects expressed P2Y 1,2,4,6,11,12,13,14 and P2X 1,4,5,6,7 receptors. NK cells stimulated with ATP, but not uridine triphosphate, increased intracellular Ca 2+ and chemokinesis. Moreover, ATP, but not uridine triphosphate, inhibited NK chemotaxis in response to CX 3CL1, whereas chemotaxis to CXCL12 was increased. CX 3CL1 elicited killing of human umbilical vein ECs and human coronary artery ECs by NK cells. However, in the presence of ATP, CX 3CL1 failed to stimulate killing of ECs. Such inhibitory effect was lost on exogenous addition of the ATP-hydrolyzing enzyme apyrase or by pharmacologic inhibition of the P2Y 11R, and correlated with increased intracellular cyclic adenosine monophosphate concentrations induced by ATP or other P2Y 11R agonists, including NAD +. Extracellular ATP regulates NK-cell cytotoxicity via P2Y 11R activation, protecting ECs from CX 3CL1-elicited NK cell-mediated killing. These findings point out the P2Y 11R as a potential target for pharmacologic intervention aimed at reducing NK-mediated vascular injury.

UR - http://www.scopus.com/inward/record.url?scp=78649489779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649489779&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-12-260828

DO - 10.1182/blood-2009-12-260828

M3 - Article

C2 - 20668227

AN - SCOPUS:78649489779

VL - 116

SP - 4492

EP - 4500

JO - Blood

JF - Blood

SN - 0006-4971

IS - 22

ER -