Hepatic catabolism of serum amyloid A during an acute phase response and chronic inflammation.
Degradation of serum amyloid A (SAA) was studied in isolated perfused livers of mice treated with either a single injection of casein to induce an acute phase response or with 14 daily casein injections to maintain chronic inflammation. Littermates administered sterile saline served as controls. Radioiodinated SAA and apolipoprotein A-I, reconstituted with high-density lipoproteins in vivo, were studied in parallel. Degradation was monitored by appearance of acid-soluble radioactivity in the perfusate. Induction of an acute phase response reduced hepatic catabolism of SAA by 14% (from 8.6 +/- 1.2% to 7.4 +/- 1.1%/g liver in 3 hr, P less than 0.05, n = 16). The acute phase response had no effect on apolipoprotein A-I degradation or bile production. Livers from animals receiving 14 daily injections of casein were 31% less active than control livers at degrading SAA (8.1 +/- 1.6%/g/3 hr for treated group vs. 11.7 +/- 2.3%/g/3 hr for control group, P less than 0.025). Apolipoprotein A-I degradation was decreased but differences were not statistically significant and bile production was the same in both treatment groups. However, livers from treated animals were larger (mean weight 1.8 g) than those from controls (1.5 g) (P less than 0.05), although amyloid fibrils were not detected by Congo red stain. The size of the degradation products was analyzed by column chromatography. Elution profiles of perfusates from livers of chronically inflamed animals contained a peak corresponding to the molecular weight of amyloid A which was not present in perfusates from control liver. We conclude that hepatic catabolism of SAA is decreased both early and late in an inflammatory response and intermediate degradation products corresponding in size to amyloid A are released into the circulation following prolonged inflammation.
Gollaher
C J
CJ
Department of Medicine, Brown University Program in Medicine, Miriam Hospital, Providence, Rhode Island 02906.
Bausserman
L L
LL
D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D002364:Caseins; D002850:Chromatography, Gel; D002908:Chronic Disease; D007249:Inflammation / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009924:Organ Culture Techniques; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D002364:Caseins; D000685:Serum Amyloid A Protein