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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4930-4937. Prepublished online as a Blood First Edition Paper on February 23, 2006; DOI 10.1182/blood-2005-10-4144. This Article Full Text (PDF) All Versions of this Article: 2005-10-4144v1 107/12/4930    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 Xu, W. Articles by van Kooten, C. Search for Related Content PubMed PubMed Citation Articles by Xu, W. Articles by van Kooten, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 18, 2005 Accepted February 2, 2006 IL-10-producing macrophages preferentially clear early apoptotic cells Wei Xu, Anja Roos, Nicole Schlagwein, Andrea M Woltman, Mohamed R Daha, and Cees van Kooten* Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands * Corresponding author; email: kooten{at}lumc.nl. Efficient clearance of apoptotic cells seems to be a prerequisite to prevent the development of autoimmunity. Here we identify that M-CSF-driven macrophages (M2) are potent phagocytes that have the unique capacity to preferentially bind and ingest early apoptotic cells. This macrophage subset has intrinsic anti-inflammatory properties, characterized by high IL-10 production in the absence of pro-inflammatory cytokines, such as IL-6 and TNF-. Importantly, whereas the IL-6 and TNF- production by GM-CSF-driven macrophages (M1) is inhibited upon uptake of apoptotic cells, the anti-inflammatory status of M2 is retained during phagocytosis. M2 were shown to use CD14 to tether apoptotic cells, whereas recognition of phosphatidylserine (PS) contributed to uptake of early apoptotic cells. M2 showed more potent macropinocytosis compared to DCs and M1, and uptake of apoptotic cells was inhibited by a macropinocytosis inhibitor. Our studies suggest that, under steady-state conditions, IL-10-producing M2 are prominently involved in the clearance of early apoptotic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Xu, S. P. Berger, L. A. Trouw, H. C. de Boer, N. Schlagwein, C. Mutsaers, M. R. Daha, and C. van Kooten Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation J. Immunol., June 1, 2008; 180(11): 7613 - 7621. [Abstract] [Full Text] [PDF] S. Nishimura, S. Takahashi, H. Kamikatahira, Y. Kuroki, D. E. Jaalouk, S. O'Brien, E. Koivunen, W. Arap, R. Pasqualini, H. Nakayama, et al. Combinatorial Targeting of the Macropinocytotic Pathway in Leukemia and Lymphoma Cells J. Biol. Chem., April 25, 2008; 283(17): 11752 - 11762. [Abstract] [Full Text] [PDF] A. Landi, L. A. Babiuk, and S. van Drunen Littel-van den Hurk High transfection efficiency, gene expression, and viability of monocyte-derived human dendritic cells after nonviral gene transfer J. Leukoc. Biol., October 1, 2007; 82(4): 849 - 860. [Abstract] [Full Text] [PDF] L. A. Trouw, A. A. Bengtsson, K. A. Gelderman, B. Dahlback, G. Sturfelt, and A. M. Blom C4b-binding Protein and Factor H Compensate for the Loss of Membrane-bound Complement Inhibitors to Protect Apoptotic Cells against Excessive Complement Attack J. Biol. Chem., September 28, 2007; 282(39): 28540 - 28548. [Abstract] [Full Text] [PDF] L. Barrett, C. Dai, J. Gamberg, M. Gallant, and M. Grant Circulating CD14-CD36+ peripheral blood mononuclear cells constitutively produce interleukin-10 J. Leukoc. Biol., July 1, 2007; 82(1): 152 - 160. [Abstract] [Full Text] [PDF] W.-H. Kwan, C. Boix, N. Gougelet, W. H. Fridman, and C. G. F. Mueller LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors J. Leukoc. Biol., July 1, 2007; 82(1): 133 - 141. [Abstract] [Full Text] [PDF] L. Arnold, A. Henry, F. Poron, Y. Baba-Amer, N. van Rooijen, A. Plonquet, R. K. Gherardi, and B. Chazaud Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis J. Exp. Med., May 14, 2007; 204(5): 1057 - 1069. [Abstract] [Full Text] [PDF]

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