Synergy between serum amyloid A and secretory phospholipase A2 suggests a vital role for an ancient protein in lipid clearance

  1. Shobini Jayaraman  Is a corresponding author
  2. Marcus Fändrich
  3. Olga Gursky
  1. Boston University School of Medicine, United States
  2. Ulm University, Germany

Abstract

Serum amyloid A (SAA) is an evolutionally conserved enigmatic biomarker of inflammation. In acute inflammation, SAA plasma levels increase ~1,000-fold suggesting a vital beneficial role. SAA increases simultaneously with secretory phospholipase A2 (sPLA2), compelling us to determine how SAA influences sPLA2 hydrolysis of lipoproteins. SAA solubilized phospholipid bilayers to form lipoproteins that provided substrates for sPLA2. Moreover, SAA sequestered free fatty acids and lysophospholipids to form stable proteolysis-resistant complexes. Unlike albumin, SAA effectively removed free fatty acids under acidic conditions, which characterize inflammation sites. Therefore, SAA solubilized lipid bilayers to generate substrates for sPLA2 and removed its bioactive products. Consequently, SAA and sPLA2 can act synergistically to remove cellular membrane debris from the injured sites, which is a prerequisite for tissue healing. We postulate that removal of lipids and their degradation products constitutes a vital primordial role of SAA in innate immunity; this role remains to be tested in vivo.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Shobini Jayaraman

    Department of Physiology and Biophysics, Boston University School of Medicine, Boston, United States
    For correspondence
    shobini@bu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1616-5347
  2. Marcus Fändrich

    Institute of Protein Biochemistry, Ulm University, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Olga Gursky

    Department of Physiology and Biophysics, Boston University School of Medicine, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (GM067260)

  • Shobini Jayaraman
  • Olga Gursky

Deutsche Forschungsgemeinschaft (FA456/15-1)

  • Marcus Fändrich

The funders provide resource to study design, data collection and submit the work for publication.

Copyright

© 2019, Jayaraman et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shobini Jayaraman
  2. Marcus Fändrich
  3. Olga Gursky
(2019)
Synergy between serum amyloid A and secretory phospholipase A2 suggests a vital role for an ancient protein in lipid clearance
eLife 8:e46630.
https://doi.org/10.7554/eLife.46630

Share this article

https://doi.org/10.7554/eLife.46630

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