The degradation of serum amyloid A protein by activated polymorphonuclear leucocytes: participation of granulocytic elastase.

To determine the role of inflammation in amyloidogenesis, we have studied the degradation of human serum amyloid A (SAA) protein by purified preparations of human blood polymorphonuclear leucocytes (PMN) and monocytes. When both PMN and monocytes were incubated in SAA-containing medium, the concentration of SAA as measured by a competitive anti-AA radioimmunoassay decreased over time. The rate of decrease of SAA was similar for both monocytes and PMN and there were no differences between four patients with amyloidosis and three normal controls. Resting PMN from normal volunteers were able to degrade SAA to smaller acid-soluble peptides within 16 hr while zymosan-activated PMN produced significant degradation within 1 hr (31%–50%). The supernatants from zymosan-treated PMN also caused marked SAA degradation within 1 hr. The following enzyme inhibitors were able to prevent degradation of SAA by PMN supernatants; phenylmethylsulphonyl fluoride, a serine esterase inhibitor; α anti-trypsin and soybean trypsin inhibitor; and acetyl-ala-ala-pro-val-chloromethyl ketone, an elastase inhibitor. The ability of a neutral lysosomal enzyme to degrade SAA was further confirmed by showing that purified PMN elastase significantly degraded I-SAA. We conclude that PMN contain one or more lysosomal enzymes capable of degrading SAA, an apoprotein of HDL serum lipoproteins. Alteration in SAA proteolysis by activated PMN may contribute to the deposition of amyloid fibrils in the tissues of patients with chronic inflammatory disease.