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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.

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IMMUNOBIOLOGY

Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated 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

From the Department of Dermatology, Venerology and Allergology, University Medical Centre Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany; the Department of Pulmonology, Theresien Hospital Mannheim, Mannheim, Germany; and GSF-Institut für Molekulare Immunologie, München, Germany.

Mammalian Glyco_18-domain–containing proteins include catalytically active chitinases and chitinase-like proteins with cytokine activity involved in host defense 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 amino acids. 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 colocalization 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 up-regulated by the Th2 cytokine IL-4 and by dexamethasone. This effect was suppressed by IFN{gamma} but not affected by IL-10. In contrast, expression of YKL-40 was induced by IFN{gamma} 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 peripheral-blood leukocytes (PBLs), and can be used to analyze the role of SI-CLP in human disorders.


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