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.
CBA/J and other inbred strains of mice that express the amyloidogenic apolipoprotein serum amyloid A (apoSAA) apoSAA2, together with apoSAA1, are susceptible to amyloid A (AA) amyloidosis, whereas CE/J mice that express a single unique isoform, apoSAACEJ, are resistant. Studies indicate that CBA/JxCE/J hybrid mice that express apoSAA2 in the presence of apoSAACEJ are protected from amyloidogenesis. To define a mechanism by which expression of apoSAACEJ may protect from AA formation in the presence of apoSAA2, 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 (1x105 cells/ml) for 30 min at 4 degreesC. The binding of 125I-r-apoSAA1, 125I-r-apoSAA2 and 125I-r-apoSAACEJ was specific and saturable, with an affinity (Kd) of about 2.8, 3.2 and 1.3 nM, respectively, and approximately 2-4x106 sites per cell. Competitive binding experiments indicate apoSAACEJ binds with higher affinity to macrophages than does either apoSAA1 or apoSAA2. We suggest that greater cellular affinity of apoSAACEJ compared to apoSAA2 may contribute to protection from AA amyloid in certain CBA/JxCE/J hybrid mice by interfering with interaction of apoSAA2 by macrophages and hence either membrane associated or intracellular degradation.
Liang
J
J
The Edith Nourse Rogers Memorial DVA Hospital, Bedford, MA 01750, USA.
Elliott-Bryant
R
R
Hajri
T
T
Sipe
J D
JD
Cathcart
E S
ES
D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D004198:Disease Susceptibility; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D020033:Protein Isoforms / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D001053:Apolipoproteins; D020033:Protein Isoforms; D000685:Serum Amyloid A Protein