Human amyloid P component: an elastase inhibitor.

Amyloid deposits almost invariably contain a pentagonal-shaped protein (a so-called pentraxin), termed amyloid P component (AP), in close apposition to the amyloid fibrils. AP is also detected alongside normal elastin fibres in skin and basement membrane. In the present studies, purified human AP was shown to inhibit the activity of porcine pancreatic elastase. The inhibition of elastolytic activity was not abolished by heating AP to 70 degrees C. Furthermore, two other human serum proteins used as controls did not inhibit elastase activity: albumin, which has a similarly acidic pI, and C-reactive protein, which is a pentraxin, sharing 50% sequence homology with AP. Enzyme kinetic studies showed that elastase treated with AP had a slower elastolytic rate than untreated elastase. The inhibitory effect of AP was reversed by high substrate (fivefold) concentration. These observations suggest that AP may function in vivo to protect elastin and amyloid fibrils from proteolytic cleavage. Indeed, this may in part account for the relative resistance of amyloid deposits to resorption and proteolysis.