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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1537-1545. Prepublished online as a Blood First Edition Paper on October 25, 2005; DOI 10.1182/blood-2005-07-2901. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: 2005-07-2901v1 107/4/1537    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Giordano, D. Articles by Clark, E. A Search for Related Content PubMed PubMed Citation Articles by Giordano, D. Articles by Clark, E. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 20, 2005 Accepted October 12, 2005 Nitric oxide and cGMP protein kinase (cGK) regulate dendritic cell migration toward the lymph node-directing chemokine CCL19a Daniela Giordano*, Dario M Magaletti, and Edward A Clark Department of Immunology, University of Washington, Seattle, WA, USA Regional Primate Research Center, University of Washington, Seattle, WA, USA Department of Immunology, University of Washington, Seattle, WA, USA; Regional Primate Research Center, University of Washington, Seattle, WA, USA * Corresponding author; email: giordano{at}u.washington.edu. Dendritic cell (DC) migration to secondary lymphoid organs is crucial for the initiation of adaptive immune responses. Although LPS up-regulates CCR7 on DCs, a second signal is required to enable them to migrate toward the chemokine CCL19 (MIP-3). We found that the nitric oxide (NO) donor NOR4 provides a signal allowing LPS-stimulated DCs to migrate toward CCL19. NO affects DC migration through both the initial activation of the cGMP/cGK (cGMP kinase) pathway and a long-term effect that reduced cGK activity via negative feedback. Indeed, migration of DCs toward CCL19, unlike migration toward CXCL12 (SDF-1), required inhibition of cGK. LPS increased both cGK expression and cGK activity as measured by phosphorylation of the key cGK target VASP (Vasodilator-Stimulated Phosphoprotein). Since cGK phosphorylation of VASP can disrupt focal adhesions and inhibit cell migration, LPS-induced VASP phosphorylation may prevent DCs from migrating without a second signal. Long-term NOR4 treatment inhibited the increase in cGK-dependent VASP phosphorylation, releasing this brake so that DCs can migrate. NO has been implicated in the regulation of autoimmunity through its effect on T cells. Our results suggest that NO regulation of DC migration and cytokine production may contribute to the protective effects of NO in autoimmune disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. van de Ven, G. L. Scheffer, A. W. Reurs, J. J. Lindenberg, R. Oerlemans, G. Jansen, J.-P. Gillet, J. N. Glasgow, A. Pereboev, D. T. Curiel, et al. A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration Blood, September 15, 2008; 112(6): 2353 - 2359. [Abstract] [Full Text] [PDF] A. Ricciardi, A. R. Elia, P. Cappello, M. Puppo, C. Vanni, P. Fardin, A. Eva, D. Munroe, X. Wu, M. Giovarelli, et al. Transcriptome of Hypoxic Immature Dendritic Cells: Modulation of Chemokine/Receptor Expression Mol. Cancer Res., February 1, 2008; 6(2): 175 - 185. [Abstract] [Full Text] [PDF]

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