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Effect of molecular size and modification pattern on the internalization of water soluble β-(1 → 3)-(1 → 4)-glucan by primary murine macrophages.

Abstract

It has been shown that -(1→3)-(1→4)-glucans (BG34) from barley and oats can trigger recognition and internalization by murine and human macrophages. Increasing evidence has suggested that macrophage recognition and internalization of BG34 are dramatically affected by the purity of BG34, the molecular weight and chemical modification. In this study, we investigated the structural features of BG34 for macrophage recognition and internalization. We prepared homogeneous BG34s of 10 kDa (BG34-10),200 kDa (BG34-200) and 500 kDa (BG34-500) with high purity, and then introduced green fluorescence FITC to the reducing ends (Re) or main chain (Mc). The results of size exclusion chromatography, 13C NMR,fluorescence microscopy, FACS analyses and MTS assay demonstrated that non-toxic BG34 of 10 kDa(BG34-10) effectively trigger macrophage internalization. The internalization was adversely affected by modifying the main chain of BG34-10 but not the reducing end. Studies using blocking antibodies on several CD11b+ and CD11b− cells suggested that CD11b may play an important role in mediating macrophage internalization of BG34-10. Quantitative RT-PCR and intracellular cytokine stain revealed that macrophages generate increased level of CD11b and TNF-α in response to BG34-10. This study for the first time demonstrated the molecular size (10 kDa) and pattern of modification (reducing end modification)for BG34-10 to mediate macrophage internalization. Since BG34 is water soluble, biocompatible and biodegradable FDA-approved material, this mechanism of BG34-10 can be used to design drug delivery system targeting macrophages.

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  • Aggregator Full Text

    • Authors

    Zhang M, Kim JA

    Institution

    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA. mxz128@case.edu

    Source

    The international journal of biochemistry & cell biology 44:6 2012 Jun pg 914-27

    MeSH

    Animals
    Carbohydrate Sequence
    Chromatography, Gel
    Chromatography, High Pressure Liquid
    Endocytosis
    Flow Cytometry
    Glucans
    Macrophages
    Magnetic Resonance Spectroscopy
    Mice
    Microscopy, Fluorescence
    Molecular Sequence Data
    Molecular Weight
    Polymerase Chain Reaction
    Solubility
    Water

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22679629