Amyloid ‘degrading factor activity': a non-specific calcium-mediated effect

Abstract

1. The clarification of turbid AA-amyloidfibril-containing agarose gels by serum has been ascribed to degradation of the fibrils and designated as ‘amyloid degrading factor'. In the present study, sera of 32 healthy blood donors and 32 patients with rheumatoid arthritis all showed ‘degrading factor activity’ against both AA amyloid fibrils and a non-fibrillar reticulin preparation of normal liver in an agarose plate assay. AL amyloid fibrils were not affected. 2. The ‘degrading activity’ of serum was correlated with the serum albumin concentration, and the effect was also given by purified human and bovine serum albumin, although it was not seen with other serum proteins. 3. The ‘degrading activity’ of serum against AA amyloid and reticulin was significantly correlated: both substrates showed low levels in a chronic disease such as rheumatoid arthritis, and reticulin inhibited ‘degrading activity’ against AA amyloid and vice versa. These results suggest the same process involves both substrates. 4. ‘Degrading activity’ was also given by EDTA and a specific calcium chelator, and was inhibited by calcium and magnesium. 5. An enzyme inhibitor showed only partial inhibition of the ‘degrading activity’ of serum, purified albumin, and EDTA. 6. These results suggest that serum ‘degrading factor activity’ is a non-specific calcium-mediated effect against AA amyloid and reticulin preparations dispersed in agarose. It may represent a change in the degree of aggregation of these proteins rather than being an effect of proteolytic degradation. This confirms the conclusions of other workers that amyloid ‘degrading factor activity’ is an phenomenon in vitro of doubtful pathophysiological significance.