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 language | English |
|---|---|
| Pages (from-to) | 4492-4500 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 116 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - Nov 25 2010 |
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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 journal › Article
}
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 -