Am J Blood Res 2013;3(1):14-28
Review Article
Regulation of innate immunity by extracellular nucleotides
Stefania Gorini, Lucia Gatta, Laura Pontecorvo, Laura Vitiello, Andrea la Sala
Laboratory of Molecular and Cellular Immunology, IRCCS San Raffaele Pisana, Italy
Received December 1, 2012; Accepted December 19, 2012; Epub January 17, 2013; Published January 25, 2013
Abstract: Extracellular ATP (eATP) is the most abundant among extracellular nucleotides and is commonly considered as a
classical danger signal, which stimulates immune responses in the presence of tissue injury. In fact, increased nucleotide
concentration in the extracellular space is generally closely associated with tissue stress or damage. However non-lytic
nucleotide release may also occur in many cell types under a variety of conditions. Extracellular nucleotides are sensed by a
class of plasma membrane receptors called P2 purinergic receptors (P2Rs). P2 receptors are expressed by all
immunological cells and their activation elicits different responses. Extracellular ATP can act as an initiator or terminator of
immune responses being able to induce different effects on immune cells depending on the pattern of P2 receptors engaged,
the duration of the stimulus and its concentration in the extracellular milieu. Millimolar (high) concentrations of extracellular
ATP, induce predominantly proinflammatory effects, while micromolar (low) doses exert mainly
tolerogenic/immunosuppressive action. Moreover small, but significant differences in the pattern of P2 receptor expression in
mice and humans confer diverse capacities of ATP in regulating the immune response. (AJBR1212001).
Keywords: Extracellular nucleotides, P2 purinergic receptors, extracellular ATP, innate immunity
Address all correspondence to:
Dr. Andrea la Sala
Laboratory of Molecular and Cellular Immunology
IRCCS San Raffaele Pisana, Via di Val Cannuta
247 00166 Rome – Italy.
Phone: +39-06-66130427; Fax: +39-06-52255561
E-mail: andrea.lasala@sanraffaele.it
Review Article
Regulation of innate immunity by extracellular nucleotides
Stefania Gorini, Lucia Gatta, Laura Pontecorvo, Laura Vitiello, Andrea la Sala
Laboratory of Molecular and Cellular Immunology, IRCCS San Raffaele Pisana, Italy
Received December 1, 2012; Accepted December 19, 2012; Epub January 17, 2013; Published January 25, 2013
Abstract: Extracellular ATP (eATP) is the most abundant among extracellular nucleotides and is commonly considered as a
classical danger signal, which stimulates immune responses in the presence of tissue injury. In fact, increased nucleotide
concentration in the extracellular space is generally closely associated with tissue stress or damage. However non-lytic
nucleotide release may also occur in many cell types under a variety of conditions. Extracellular nucleotides are sensed by a
class of plasma membrane receptors called P2 purinergic receptors (P2Rs). P2 receptors are expressed by all
immunological cells and their activation elicits different responses. Extracellular ATP can act as an initiator or terminator of
immune responses being able to induce different effects on immune cells depending on the pattern of P2 receptors engaged,
the duration of the stimulus and its concentration in the extracellular milieu. Millimolar (high) concentrations of extracellular
ATP, induce predominantly proinflammatory effects, while micromolar (low) doses exert mainly
tolerogenic/immunosuppressive action. Moreover small, but significant differences in the pattern of P2 receptor expression in
mice and humans confer diverse capacities of ATP in regulating the immune response. (AJBR1212001).
Keywords: Extracellular nucleotides, P2 purinergic receptors, extracellular ATP, innate immunity
Address all correspondence to:
Dr. Andrea la Sala
Laboratory of Molecular and Cellular Immunology
IRCCS San Raffaele Pisana, Via di Val Cannuta
247 00166 Rome – Italy.
Phone: +39-06-66130427; Fax: +39-06-52255561
E-mail: andrea.lasala@sanraffaele.it
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