A unique amyloidogenic apolipoprotein serum amyloid A (apoSAA) isoform expressed by the amyloid resistant CE/J mouse strain exhibits higher affinity for macrophages than apoSAA1 and apoSAA2 expressed by amyloid susceptible CBA/J mice

Abstract CBA/J and other inbred strains of mice that express the amyloidogenic apolipoprotein serum amyloid A (apoSAA) apoSAA 2 , together with apoSAA 1 , are susceptible to amyloid A (AA) amyloidosis, whereas CE/J mice that express a single unique isoform, apoSAA CEJ , are resistant. Studies indicate that CBA/J×CE/J hybrid mice that express apoSAA 2 in the presence of apoSAA CEJ are protected from amyloidogenesis. To define a mechanism by which expression of apoSAA CEJ may protect from AA formation in the presence of apoSAA 2 , binding of recombinant apoSAA (r-apoSAA) isoforms, validated by N-terminal sequencing, to a murine macrophage cell line was investigated. Maximal specific binding occurred after incubation of radiolabeled apoSAA with IC-21 macrophages (1×10 5 cells/ml) for 30 min at 4°C. The binding of 125 I-r-apoSAA 1 , 125 I-r-apoSAA 2 and 125 I-r-apoSAA CEJ was specific and saturable, with an affinity ( K d ) of about 2.8, 3.2 and 1.3 nM, respectively, and approximately 2–4×10 6 sites per cell. Competitive binding experiments indicate apoSAA CEJ binds with higher affinity to macrophages than does either apoSAA 1 or apoSAA 2 . We suggest that greater cellular affinity of apoSAA CEJ compared to apoSAA 2 may contribute to protection from AA amyloid in certain CBA/J×CE/J hybrid mice by interfering with interaction of apoSAA 2 by macrophages and hence either membrane associated or intracellular degradation.