Synergy between serum amyloid A and secretory phospholipase A2

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 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 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.