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-s usceptible CBA/J mice, amyloid-resistant CE/J mice and their amyloid-r esistant CBA/J x CE/J F-1 progeny was investigated in vitro. Serum amy loid 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 fr om CE/J mice did not occur. Degradation of apoSAA by RPCS and CDM from CBA/J x CE/J F-1 hybrid mice was indistinguishable from that by RPCS and CDM from the CBA/J parent. Intermediate fragments were not detecte d with either RPCS or CDM from CBA/J mice or CBA/J x CE/J F-1 hybrid m ice. Degradation of apoSAA was inhibited by phenylmethanylsulfonyl flu oride (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 w as significantly different, the genetic study did not support the hypo thesis that there was direct linkage between impaired degradation of a poSAA-HDL in the CE/J mouse strain and protection against amyloid fibr il formation. As amyloid resistance in CBA/J x CE/J F-1 hybrid mice is not attributable to failure to express the amyloidogenic isoform apoS AA(2), the study supports the original hypothesis that amyloid resista nce may be linked to expression of apoSAA(cej).