MOUSE SERUM AMYLOID-A PROTEIN (SAA(5)) STRUCTURE AND EXPRESSION

A novel member of the mouse serum amyloid A protein family, SAA(5), ha s been identified as a normal apolipoprotein component of non-acute-ph ase high density lipoprotein (HDL). The structure of SAA(5) was derive d from a clone isolated from a normal Balb/c liver cDNA library. The c lone predicts a pre-SAA(5) molecule of 130 residues from which an 18-r esidue leader peptide is cleaved. The mature molecule has an octapepti de insert spanning from position 70 to 77. Similar inserts are found i n human C-SAA and, paradoxically, in acute-phase SAA molecules of a nu mber of other species. There is 48% amino acid identity between apo-SA A(5) and the other mouse SAA proteins and 57% identity between the hum an C-SAA and apo-SAA(5). The SAA, mRNA is three times larger than prev iously identified SAA mRNAs. Although SAA(5) is constitutively express ed in the liver, it has a rapid albeit muted response to inflammatory stimuli. The increase of SAA(5) mRNA is due to increased transcription rather than mRNA stabilization. Plasma SAA(5) levels during the acute phase are biphasic, either because of translational control or displa cement from HDL and rapid clearance. We propose that constitutive SAAs (SAA(5)) on normal HDL contribute to its normal physiological role, w hereas the dramatically inducible family members (SAA(1), SAA(2), SAA( 3)) equip this particle for an altered functional role during inflamma tion.