HDL/Apolipoprotein A-I Binds to Macrophage-Derived Progranulin and Suppresses its Conversion into Proinflammatory Granulins

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Author(s)

    • Okura Hanayuki
    • Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation.|Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine.|Research Fellow of the Japan Society for the Promotion of Science.
    • Matsuyama Akifumi
    • Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation.
    • Yamashita Shizuya
    • Division of Cardiology, Department of Internal Medicine, Osaka University Graduate School of Medicine.
    • Ohama Tohru
    • Division of Cardiology, Department of Internal Medicine, Osaka University Graduate School of Medicine.
    • Saga Ayami
    • Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation.
    • Yamamoto-Kakuta Aya
    • Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation.
    • Hamada Yoko
    • Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation.
    • Sougawa Nagako
    • Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation.
    • Ohyama Reiko
    • Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation.
    • Sawa Yoshiki
    • Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine.

Abstract

Aim: HDL has anti-inflammatory effects on macrophages, although the mechanism of action remains unclear. We hypothesized that HDL suppresses the conversion of macrophage-secreted factors into proinflammatory factors via binding, and tried to identify the factor that could form a complex with HDL and/or apolipoprotein (apo) A-I.<BR>Methods and Results: In conditioned media obtained from human monocyte-derived macrophages, we found an apo A-I binding protein and identified the protein as progranulin/proepithelin/acrogranin/PCDGF. Co-immunoprecipitation analysis showing that progranulin binds and forms a complex with apo A-I and the presence of progranulin in the HDL fraction in the sera indicated that progranilin is a novel apolipoprotein. Conditioned media of HEK293 cells transfected with progranulin augmented the expression of TNF-alpha and IL-1-beta on macrophages, but these effects of progranulin were inhibited by co-incubation with HDL or apo A-I. Anti-progranulin antibodies also reduced the expression of TNF-alpha and IL-1-beta on macrophages. Granulins as conversion products derived from progranilin increased TNF-alpha and IL-1-beta expression and the effects were not suppressed by HDL.<BR>Conclusions: Our results suggest that the anti-inflammatory effects of HDL on macrophages might be due to suppression of the conversion of progranulin into proinflammatory granulins by forming a complex.

Journal

  • Journal of Atherosclerosis and Thrombosis

    Journal of Atherosclerosis and Thrombosis 17(6), 568-577, 2010

    Japan Atherosclerosis Society

Codes

  • NII Article ID (NAID)
    130004845317
  • Text Lang
    ENG
  • ISSN
    1340-3478
  • Data Source
    J-STAGE 
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