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

Blood. 2006 Apr 15;107(8):3221-8. doi: 10.1182/blood-2005-07-2843. Epub 2005 Dec 15.

Abstract

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 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 peripheral-blood leukocytes (PBLs), and can be used to analyze the role of SI-CLP in human disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / immunology
  • Anti-Inflammatory Agents / pharmacology
  • Bronchoalveolar Lavage Fluid
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cell Adhesion Molecules, Neuronal / biosynthesis
  • Cell Adhesion Molecules, Neuronal / immunology*
  • Cells, Cultured
  • Chitinases / biosynthesis
  • Chitinases / genetics
  • Chitinases / immunology*
  • Cytokines / immunology
  • Cytokines / pharmacology
  • Dexamethasone / immunology
  • Dexamethasone / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Expression Regulation, Enzymologic / immunology*
  • Golgi Apparatus / enzymology
  • Golgi Apparatus / immunology
  • Humans
  • Inflammation / enzymology
  • Inflammation / immunology
  • Lysosomes / immunology*
  • Macrophage Activation / drug effects
  • Macrophage Activation / genetics
  • Macrophage Activation / immunology*
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / enzymology
  • Macrophages, Alveolar / immunology*
  • Protein Structure, Tertiary / genetics
  • Protein Transport / genetics
  • Protein Transport / immunology
  • Receptors, Lymphocyte Homing / biosynthesis
  • Receptors, Lymphocyte Homing / immunology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • Anti-Inflammatory Agents
  • CHID1 protein, human
  • Carrier Proteins
  • Cell Adhesion Molecules, Neuronal
  • Cytokines
  • Receptors, Lymphocyte Homing
  • STAB1 protein, human
  • Dexamethasone
  • Chitinases