Blood Journal
Leading the way in experimental and clinical research in hematology

Immunoregulation through extracellular nucleotides

  1. Laura Vitiello1,
  2. Stefania Gorini1,
  3. Giuseppe Rosano2, and
  4. Andrea la Sala1
  1. 1Laboratory of Molecular and Cellular Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy; and
  2. 2Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy


Extracellular ATP (eATP), the most abundant among nucleotides, can act as a mediator during inflammatory responses by binding to plasmamembrane P2 purinergic receptors, which are widely expressed on cells of the immune system. eATP is generally considered as a classical danger signal, which stimulates immune responses in the presence of tissue damage. Converging evidence from several studies using murine models of chronic inflammation have supported this hypothesis; however, the role of eATP in the regulation of human immune function appears to be more complex. Chronic stimulation with micromolar eATP concentrations inhibits the proliferation of T and NK lymphocytes and enhances the capacity of dendritic cells to promote tolerance. The effect of eATP depends on multiple factors, such as the extent of stimulation, eATP concentration, presence/absence of other mediators in the microenvironment, and pattern of P2 receptor engagement. Small but significant differences in the pattern of P2 receptor expression in mice and humans confer the diverse capacities of ATP in regulating the immune response. Such diversity, which is often overlooked, should therefore be carefully considered when evaluating the role of eATP in human inflammatory and autoimmune diseases.

  • Submitted January 25, 2012.
  • Accepted May 29, 2012.
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