Characterization of constitutive human serum amyloid A protein (SAA₄) as an apolipoprotein

Serum amyloid A proteins (SAAs), a family of homologous molecules, are apolipoproteins of high density lipoprotein (HDL). They can be divided into two groups. The first group comprises the well-characterized acute phase SAAs that associate with HDL during inflammation, thereby remodeling the HDL particle by displacing apolipoprotein (apo)A-I. The second group consists of the recently discovered constitutive SAAs, mouse SAA₃ and human SAA₄. They exist as minor apolipoproteins on HDL but constitute more than 90% of the total SAA during homeostasis. We have characterized human SAA₄ as an apolipoprotein. During homeostasis, SAA₄ is synthesized only in the liver. Purification of SAA₄ has been described and its plasma concentration has been established at 55 ± 13 μg/ml in 26 healthy individuals. It was present on all HDL density classes and very low density lipoprotein (VLDL) but was absent from low density lipoprotein (LDL). Using two-dimensional electrophoresis and phosphorimaging, SAA₄ was found to be associated with a specific subpopulation of truly three HDL particles, not involved in the initial cholesterol transfer from cells.