Systemic reactive amyloidosis is a rare but frequently fatal complication of chronic inflammatory diseases. The disorder appears to arise when a normal blood protein, serum amyloid A (SAA), is incompletely catabolized and deposited as amyloid A (AA) in tissues. SAA, which is transported with the plasma high density lipoproteins (HDL), has been characterized. We propose to investigate the transport of SAA in human plasma, to study the metabolism of SAA in subhuman species, and to directly test the hypothesis that SAA is the precursor of AA. We will define the spectrum of SAA-containing particles in the plasma of volunteers suffering an experimental acute-phase response and in the plasma of patients with acute and chronic inflammatory diseases and familial HDL deficiency (Tangier disease). Subhuman primates will be used to determine the magnitude and source of SAA transported in monkey lymph and the fate of SAA bound to chylomicrons and HDL. SAA tissue clearance and/or deposition will be studied in normal mice and in animals in the pre-amyloid and deposition phases of amyloidosis. In many studies we will use recently introduced radioactive tracers that remain intracellular after tissue uptake. Tissue sites of normal SAA clearance will be identified, and studies will be undertaken using the isolated, perfused rabbit liver and liver cells in monolayer culture to define the normal mechanisms of SAA catabolism. The dependence of SAA clearance on extracellular proteolysis will be examined and we will attempt to identify the clotting factor which activates an SAA protease in serum. Finally, we will seek direct evidence that SAA is converted to AA.
| Gollaher, C J; Bausserman, L L (1990) Hepatic catabolism of serum amyloid A during an acute phase response and chronic inflammation. Proc Soc Exp Biol Med 194:245-50 |
| Bausserman, L L; Sadaniantz, A; Saritelli, A L et al. (1989) Time course of serum amyloid A response in myocardial infarction. Clin Chim Acta 184:297-305 |
| Bausserman, L L; Bernier, D N; McAdam, K P et al. (1988) Serum amyloid A and high density lipoproteins during the acute phase response. Eur J Clin Invest 18:619-26 |
| Bausserman, L L; Saritelli, A L; Van Zuiden, P et al. (1987) Degradation of serum amyloid A by isolated perfused rat liver. J Biol Chem 262:1583-9 |
| Herbert, P N; Bausserman, L L; Lynch, K M et al. (1987) Homologues of the human C and A apolipoproteins in the Macaca fascicularis (cynomolgus) monkey. Biochemistry 26:1457-63 |
