Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is upregulated in alternatively activated macrophages and secreted via lysosomal pathway

Kzhyshkowska J, Mamidi S, Gratchev A, Kremmer E, Schmuttermaier C, Krusell L, Haus G, Utikal J, Schledzewski K, Scholtze J and Goerdt S
Source: Blood
Publication Date: (2006)
Issue: 107(8): 3221-8
Research Area:
Immunotherapy / Hematology
Cells used in publication:
Macrophage, human
Species: human
Tissue Origin: blood
Nucleofector® I/II/2b
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 IFNgamma but not affected by IL-10. In contrast, expression of YKL-40 was induced by IFNgamma 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.