Degradation of serum amyloid A in amyloid-susceptible and amyloid-resistant mouse strains.
Degradation of serum amyloid A (apoSAA) by resident peritoneal cells (RPCS) and conditioned medium (CDM), prepared with RPCS, from amyloid-susceptible CBA/J mice, amyloid-resistant CE/J mice and their amyloid-resistant CBA/J x CE/J F1 progeny was investigated in vitro. Serum amyloid A was derived from murine acute phase (AP) plasma and associated with high density lipoprotein (HDL). Degradation of apoSAA by RPCS and CDM from CBA/J mice was complete while degradation by RPCS and CDM from CE/J mice did not occur. Degradation of apoSAA by RPCS and CDM from CBA/J x CE/J F1 hybrid mice was indistinguishable from that by RPCS and CDM from the CBA/J parent. Intermediate fragments were not detected with either RPCS or CDM from CBA/J mice or CBA/J x CE/J F1 hybrid mice. Degradation of apoSAA was inhibited by phenylmethanylsulfonyl fluoride (PMSF) indicating that the enzyme, secreted into the fluid phase, was a serine esterase. Unlike apoSAA, HDL-associated apoA-1 remained intact. It was thus concluded that while selective degradation of HDL-associated apoSAA (apoSAA-HDL) by RPCS from the CBA/J and CE/J mice was significantly different, the genetic study did not support the hypothesis that there was direct linkage between impaired degradation of apoSAA-HDL in the CE/J mouse strain and protection against amyloid fibril formation. As amyloid resistance in CBA/J x CE/J F1 hybrid mice is not attributable to failure to express the amyloidogenic isoform apoSAA2, the study supports the original hypothesis that amyloid resistance may be linked to expression of apoSAAcej.
Elliott-Bryant
R
R
Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA 01730, USA.
Liang
J S
JS
Sipe
J D
JD
Cathcart
E S
ES
D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D000682:Amyloid; D001053:Apolipoproteins; D011480:Protease Inhibitors; D011498:Protein Precursors; D000685:Serum Amyloid A Protein