A UNIQUE AMYLOIDOGENIC APOLIPOPROTEIN SERUM AMYLOID-A (APOSAA) ISOFORM EXPRESSED BY THE AMYLOID RESISTANT CE J MOUSE STRAIN EXHIBITS HIGHERAFFINITY FOR MACROPHAGES THAN APOSAA(1) AND APOSAA(2) EXPRESSED BY AMYLOID SUSCEPTIBLE CBA/J MICE/

CBA/J and other inbred strains of mice that express the amyloidogenic apolipoprotein serum amyloid A (apoSAA) apoSAA(2), together with apoSA A(1), are susceptible to amyloid A (AA) amyloidosis, whereas CE/J mice that express a single unique isoform, apoSAA(CEJ), are resistant., St udies indicate that CBA/JxCE/J hybrid mice that express apoSAA(2) in t he presence of apoSAA(CEJ) are protected from amyloidogenesis. To defi ne a mechanism by which expression of apoSAA(CEJ) may protect from AA formation in the presence of apoSPLA(2), binding of recombinant apoSAA (r-apoSAA) isoforms, validated by N-terninal sequencing, to a murine macrophage cell line was investigated. Maximal specific binding occurr ed after incubation of radiolabeled apoSAA with IC-21 macrophages (1x1 0(5) cells/ml) for 30 min at 4 degrees C. The binding of I-125-r-apoSA A(1), I-125-r-apoSAA(2) and I-125-r-apoSAA(CEJ) was specific and satur able, with an affinity (K-d) of about 2.8, 3.2 and 1.3 nM, respectivel y, and approximately 2-4 x 10(6) sites per cell. Competitive binding e xperiments indicate apoSAA(CEJ) binds with higher affinity to macropha ges than does either apoSAA(1) or apoSAA(2). We suggest that greater c ellular affinity of apoSAA(CEJ) compared to apoSAA(2) may contribute t o protection from AA amyloid in certain CBA/J X CE/J hybrid mice by in terfering with interaction of apoSAA(2) by macrophages and hence eithe r membrane associated or intracellular degradation. (C) 1998 Published by Elsevier Science B.V. All rights reserved.