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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3580-3589. Prepublished online as a Blood First Edition Paper on August 1, 2006; DOI 10.1182/blood-2006-03-013334. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2006-03-013334v1 108/10/3580    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Krispin, A. Articles by Mevorach, D. Search for Related Content PubMed PubMed Citation Articles by Krispin, A. Articles by Mevorach, D. Related Collections Phagocytes Apoptosis Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states Alon Krispin, Yaniv Bledi, Mizhir Atallah, Uriel Trahtemberg, Inna Verbovetski, Efrat Nahari, Orly Zelig, Michal Linial, and Dror Mevorach From the Laboratory for Cellular and Molecular Immunology, Rheumatology Unit Department of Medicine, and Transfusion Medicine Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; and the Department of Biological Chemistry, Life Science Institute, the Hebrew University, Jerusalem, Israel. Apoptotic cells were shown to induce dendritic cell immune tolerance. We applied a proteomic approach to identify molecules that are secreted from apoptotic monocytes, and thus may mediate engulfment and immune suppression. Supernatants of monocytes undergoing apoptosis were collected and compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and differentially expressed proteins were identified using tandem mass spectrometry. Thrombospondin-1 (TSP-1) and its cleaved 26-kDa heparin-binding domain (HBD) were identified. We show that TSP-1 is expressed upon induction of monocyte apoptosis in a caspase-dependent pattern and the HBD is cleaved by chymotrypsin-like serine protease. We further show that CD29, CD36, CD47, CD51, and CD91 simultaneously participate in engulfment induction and generation of an immature dendritic cell (iDC) tolerogenic and phagocytic state. We conclude that apoptotic cell TSP-1, and notably its HBD, creates a signalosome in iDCs to improve engulfment and to tolerate engulfed material prior to the interaction with apoptotic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. B. Maxhimer, D. R. Soto-Pantoja, L. A. Ridnour, H. B. Shih, W. G. DeGraff, M. Tsokos, D. A. Wink, J. S. Isenberg, and D. D. Roberts Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling Science Translational Medicine, October 21, 2009; 1(3): 3ra7 - 3ra7. [Abstract] [Full Text] [PDF] M.-L. del Rio, J.-I. Rodriguez-Barbosa, J. Bolter, M. Ballmaier, O. Dittrich-Breiholz, M. Kracht, S. Jung, and R. Forster CX3CR1+c-kit+ Bone Marrow Cells Give Rise to CD103+ and CD103- Dendritic Cells with Distinct Functional Properties J. Immunol., November 1, 2008; 181(9): 6178 - 6188. [Abstract] [Full Text] [PDF] M. A. Pallero, C. A. Elzie, J. Chen, D. F. Mosher, and J. E. Murphy-Ullrich Thrombospondin 1 binding to calreticulin-LRP1 signals resistance to anoikis FASEB J, November 1, 2008; 22(11): 3968 - 3979. [Abstract] [Full Text] [PDF]

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