Synergy between serum amyloid A and secretory phospholipase A<sub>2</sub>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31111824.
- Also identified by DOI 10.7554/eLife.46630 and PMC identifier 6557629.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Serum amyloid A (SAA) is an evolutionally conserved enigmatic biomarker of inflammation. In acute inflammation, SAA plasma levels increase ~1,000 fold, suggesting that this protein family has a vital beneficial role. SAA increases simultaneously with secretory phospholipase A<sub>2</sub> (sPLA<sub>2</sub>), compelling us to determine how SAA influences sPLA<sub>2</sub> hydrolysis of lipoproteins. SAA solubilized phospholipid bilayers to form lipoproteins that provided substrates for sPLA<sub>2</sub>. 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 sPLA<sub>2</sub> and removed its bioactive products. Consequently, SAA and sPLA<sub>2</sub> can act synergistically to remove cellular membrane debris from injured sites, which is a prerequisite for tissue healing. We postulate that the 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.
Medical subject headings
- Phospholipases A2, Secretory
- Serum Amyloid A Protein