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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3221-3228. Prepublished online as a Blood First Edition Paper on December 15, 2005; DOI 10.1182/blood-2005-07-2843. This Article Full Text (PDF) All Versions of this Article: 2005-07-2843v1 107/8/3221    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 Kzhyshkowska, J. Articles by Goerdt, S. Search for Related Content PubMed PubMed Citation Articles by Kzhyshkowska, J. Articles by Goerdt, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 18, 2005 Accepted November 29, 2005 Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is upregulated in alternatively activated macrophages and secreted via lysosomal pathway Julia Kzhyshkowska*, Srinivas Mamidi, Alexei Gratchev, Elisabeth Kremmer, Christina Schmuttermaier, Liis Krusell, Georg Haus, Jochen Utikal, Kai Schledzewski, Joachim Scholtze, and Sergij Goerdt Department of Dermatology, Venerology and Allergology, University Medical Centre Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany GSF-Institut fuer Molekulare Immunologie, Munchen, Germany Department of Pulmonology, Theresien Hospital, Mannheim, Germany * Corresponding author; email: julia-k{at}gmx.net. Mammalian Glyco_18-domain-containing proteins include catalytically active chitinases and chitinase-like proteins with cytokine activity involved in host defence and Th2-type inflammatory reactions. Here we describe a novel human Glyco_18 domain containing protein, SI-CLP, as an interacting partner of the endocytic/sorting receptor stabilin-1. Similarly to the chitinase-like cytokines YKL-39, YKL-40 and YM1/2, SI-CLP lacks a chitin-binding domain and catalytic aminoacids. Using a novel mAb 1C11, we demonstrated that SI-CLP is sorted into late endosomes and secretory lysosomes in human alternatively activated macrophages. The direct interaction of SI-CLP with stabilin-1, their co-localisation in the trans-Golgi network, and the reduced sorting of SI-CLP into lysosomes in macrophages treated with stabilin-1 siRNA suggest that stabilin-1 is involved in intracellular sorting of SI-CLP. Expression of SI-CLP in macrophages was strongly upregulated by the Th2 cytokine IL-4 and by dexamethasone. This effect was suppressed by IFN but not affected by IL-10. In contrast, expression of YKL-40 was induced by IFN and suppressed by dexamethasone. Macrophages treated with IL-4 secreted SI-CLP, while costimulation with dexamethasone blocked secretion and resulted in intracellular accumulation of SI-CLP. The 1C11 mAb detected SI-CLP in human bronchoalveolar lavage and PBLs, and can be used to analyze the role of SI-CLP in human disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Zhang, A. Gratchev, V. Riabov, S. Mamidi, C. Schmuttermaier, L. Krusell, E. Kremmer, G. Workman, E. H. Sage, S. Jalkanen, et al. A Novel GGA-Binding Site Is Required for Intracellular Sorting Mediated by Stabilin-1 Mol. Cell. Biol., November 15, 2009; 29(22): 6097 - 6105. [Abstract] [Full Text] [PDF] S.-Y. Park, M.-Y. Jung, S.-J. Lee, K.-B. Kang, A. Gratchev, V. Riabov, J. Kzhyshkowska, and I.-S. Kim Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages J. Cell Sci., September 15, 2009; 122(18): 3365 - 3373. [Abstract] [Full Text] [PDF] A. Gratchev, J. Kzhyshkowska, S. Kannookadan, M. Ochsenreiter, A. Popova, X. Yu, S. Mamidi, E. Stonehouse-Usselmann, I. Muller-Molinet, L. Gooi, et al. Activation of a TGF-{beta}-Specific Multistep Gene Expression Program in Mature Macrophages Requires Glucocorticoid-Mediated Surface Expression of TGF-{beta} Receptor II J. Immunol., May 15, 2008; 180(10): 6553 - 6565. [Abstract] [Full Text] [PDF] J. Kzhyshkowska, A. Gratchev, C. Schmuttermaier, H. Brundiers, L. Krusell, S. Mamidi, J. Zhang, G. Workman, E. H. Sage, C. Anderle, et al. Alternatively Activated Macrophages Regulate Extracellular Levels of the Hormone Placental Lactogen via Receptor-Mediated Uptake and Transcytosis J. Immunol., March 1, 2008; 180(5): 3028 - 3037. [Abstract] [Full Text] [PDF] M. G. Nair, K. J. Guild, and D. Artis Novel Effector Molecules in Type 2 Inflammation: Lessons Drawn from Helminth Infection and Allergy J. Immunol., August 1, 2006; 177(3): 1393 - 1399. [Full Text] [PDF] H. F. Bigg, R. Wait, A. D. Rowan, and T. E. Cawston The Mammalian Chitinase-like Lectin, YKL-40, Binds Specifically to Type I Collagen and Modulates the Rate of Type I Collagen Fibril Formation J. Biol. Chem., July 28, 2006; 281(30): 21082 - 21095. [Abstract] [Full Text] [PDF]

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