Synergy between serum amyloid A and secretory phospholipase A(2).

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(2) (sPLA(2)), compelling us to determine how SAA influences sPLA(2) hydrolysis of lipoproteins. SAA solubilized phospholipid bilayers to form lipoproteins that provided substrates for sPLA(2). 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(2) and removed its bioactive products. Consequently, SAA and sPLA(2) 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.