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(Journal of Leukocyte Biology. 2003;73:339-343.)
© 2003 by Society for Leukocyte Biology

Alerting and tuning the immune response by extracellular nucleotides

Andrea la Sala*, Davide Ferrari{dagger}, Francesco Di Virgilio{dagger}, Marco Idzko{ddagger}, Johannes Norgauer{ddagger} and Giampiero Girolomoni§

* Immune Cell Interaction Unit, Mucosal Immunity Section, Laboratory of Clinical Investigation, NIAID, National Institutes of Health, Bethesda, Maryland;
{dagger} Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Italy;
{ddagger} Department of Experimental Dermatology, University of Freiburg, Germany; and
§ Laboratory of Immunology, Istituto Dermopatico dell’Immacolata, IRCCS, Rome, Italy

Correspondence: Dr. Andrea la Sala, Immune Cell Interaction Unit, Mucosal Immunity Section, Laboratory of Clinical Investigation, NIAID, NIH, 10 Center Drive, 11/N214, Bethesda, MD 20892. E-mail: alasala{at}niaid.nih.gov

The interplay between pro- and anti-inflammatory mechanisms during inflammatory and immune responses is critical for avoiding excessive tissue damage. Extracellular nucleotides (e.g., adenosine 5'-triphosphate) may represent constitutive signals that can alert the immune system of abnormal cell death. Relatively high doses of nucleotides induce rapid release of proinflammatory mediators and favor pathogen killing. However, recent findings on antigen presenting cells, particularly dendritic cells, revealed a more complex role for these molecules. Chronic exposure to low-dose nucleotides can redirect cellular responses to prototypic activation stimuli, leading to suppressed inflammation and immune deviation.

Key Words: dendritic cell • monocyte • ATP • chemokine • IL-12




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