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Blood, 4 June 2009, Vol. 113, No. 23, pp. 5848-5856. Prepublished online as a Blood First Edition Paper on April 1, 2009; DOI 10.1182/blood-2008-12-194597. This Article Full Text Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: blood-2008-12-194597v1 113/23/5848    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Salogni, L. Articles by Sozzani, S. PubMed PubMed Citation Articles by Salogni, L. Articles by Sozzani, S. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14 Laura Salogni1, Tiziana Musso2, Daniela Bosisio1, Massimiliano Mirolo3, Venkatakrishna R. Jala4, Bodduluri Haribabu4, Massimo Locati3, and Silvano Sozzani1 1 Department of Biomedical Sciences and Biotechnology, Section of General Pathology and Immunology, University of Brescia, Brescia, Italy; 2 Department of Public Health and Microbiology, University of Torino, Torino, Italy; 3 Laboratory of Leukocyte Biology, Department of Translational Medicine, University of Milan, Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano, Italy; and 4 James Graham Brown Cancer Center, University of Louisville, KY Activin A is a dimeric protein, member of the transforming growth factor (TGF)–β family that plays a crucial role in wound repair and in fetal tolerance. Emerging evidence also proposes activin A as a key mediator in inflammation. This study reports that activin A induces the directional migration of immature myeloid dendritic cells (iDCs) through the activation of ALK4 and ActRIIA receptor chains. Conversely, activin A was not active on plasmacytoid dendritic cells (DCs) or mature myeloid DCs. iDC migration to activin A was phosphatidylinositol 3-kinase –dependent, Bordetella pertussis toxin– and cycloheximide-sensitive, and was inhibited by M3, a viral-encoded chemokine-binding protein. In a real-time video microscopy-based migration assay, activin A induced polarization of iDCs, but not migration. These characteristics clearly differentiated the chemotactic activities of activin A from TGF-β and classic chemokines. By the use of combined pharmacologic and low-density microarray analysis, it was possible to define that activin-A–induced migration depends on the selective and polarized release of 2 chemokines, namely CXC chemokine ligands 12 and 14. This study extends the proinflammatory role of activin A to DC recruitment and provides a cautionary message about the reliability of the in vitro chemotaxis assays in discriminating direct versus indirect chemotactic agonists. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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