Serum amyloid A, in vivo splenic cholesterol export and its potential implications in hemolytic disorders

A model to examine the in vivo relationship of acute phase serum amyloid A (SAA) to spleen cholesterol mobilisation was devised. Reticuloendothelial cells in vivo were loaded with a known quantity of cholesterol (1.5 mg) by infusing fragmented red blood cell membranes, which consist of approximately 50% cholesterol by dry weight. Following infusion, 7% of the infused cholesterol was in the spleen and significantly increased (by 35%) spleen cholesterol concentration above the baseline. An acute inflammatory reaction was induced by the subcutaneous injection of AgNO(3) which also raised spleen cholesterol values, but not significantly. Both treatments were also administered together and the increase in spleen cholesterol concentration after 1 h was equivalent to the sum of the individual treatments. In all the treatment groups, the spleen cholesterol concentration and the plasma SAA values were then followed over a period of 24 h. In all treatment groups the spleen cholesterol values fell to baseline values primarily between 18 and 24 h which coincided with significantly raised levels of plasma SAA. In the case of the dual treatment, between 4 and 18 h, SAA increased from 92.1 +/- 12.3 to 478 +/- 58.3 microg/ml, respectively and depletion of spleen cholesterol occurred gradually reaching baseline values after 24 h. The significant flux of cholesterol though the spleen raises the distinct possibility that the spleen is much more involved in cholesterol metabolism than previously appreciated. Furthermore, the speed with which plasma SAA increases following the infusion of fragmented red blood cell membranes and the role that SAA plays in cholesterol mobilisation raise issues that may be relevant to alterations in plasma acute phase protein and lipid parameters in patients undergoing transfusions or suffering from hemolytic disorders.