Histidine-rich glycoprotein and stanniocalcin-2 high affinity interactions with inflammatory cells

• AbstractThe plasma protein Histidine-rich protein (HRG), is implicated in macrophage polarization to an M1 antitumoral phenotype. The broadly expressed, secreted protein Stanniocalcin 2 (STC2), also implicated in tumor inflammation, is an HRG interaction partner. To assess the effects of HRG and STC2 on inflammation in a biologically relevant model, binding of recombinant HRG and STC2 preparations to each other and to cells was explored using quartz crystal microbalance (QCM) methodology. Protein functionality was tested in a phagocytosis assay. Stimulation with HRG increased phagocytosis in U937 cells while STC2 suppressed HRG-induced phagocytosis. Binding of HRG to STC2 measured using QCM showed an affinity in the nanomolar range and occurred in a conformation-dependent manner. Both HRG and STC2 bound individually and in combination to monocytic U937 cells with higher efficiency after vitamin D3-induced differentiation. HRG, but not STC2, also bound to formaldehyde-fixed U937 cells irrespective of differentiation stage, potentially through heparan sulphate. These data show that binding of HRG to STC2 is specific and conformation-dependent, and HRG and STC2 bind to separate sites on U937 cells, suggesting that they exert their effects through distinct cell surface entities.  

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NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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