Definition
Amyloid P component (AP) is a glycoprotein which is found in tissue deposits of all types of amyloid and is identical to and derived from serum amyloid P component (SAP).
Discovery
AP was not originally detected in normal, non-amyloid-containing tissues, but Schneider and Loos1 observed that fluoresceinated anti-AP antibodies stained vascular and perivascular structures in sections of a number of normal tissues and suggested that AP may be a form of type IV, basement-membrane-type collagen.
Structural Characteristics
AP is a glycoprotein composed of a pair of noncovalently bound pentameric discs with a subunit size of 23-25 kDa. Each subunit consists of 204 residues, a single disulfide bridge linking Cys 36 to Cys 95, and a carbohydrate moiety attached to Asn 32. The precursor of AP is the SAP. It shares 52% homology with the amended sequence of human C-reactive protein, an acute phase protein, and 68% homology with the Syrian hamster "female protein," another acute phase protein whose response is modulated by sex steroids. AP/SAP, C-reactive protein, and female protein belong to a family of plasma proteins called pentraxins and their considerable sequence homology is probably the result of gene duplication2.
Mode of Action
AP is apparently indistinguishable from a normal serum protein, SAP which in turn is closely related to, though distinct from, C-reactive protein, the classical acute phase reactant. Earlier report show that in mice3, though not in man, SAP behaves as an acute phase reactant and that its serum level remains persistently elevated during induction of amyloidosis by repeated injections of casein4. Human SAP undergoes calcium-dependent binding to both primary (AL) and secondary (AA) amyloid fibrils in vitro and it has been suggested that EDTA treatment may dissociate AP from a more intimate association with fibril proteins than had previously been suspected5. Furthermore, recent quantitative estimates of the relative amounts of AP and fibril protein in human amyloid indicate that, far from being a trace constituent, the ratio by weight of AP to isolated fibrils can be as high as 1:7. These observations taken together raise the possibility that SAP/AP may be involved in the pathogenesis of amyloidosis.
Functions
Association of amyloid P component with complement proteins in neurologically diseased brain tissue: In a study AP was detected in a number of lesions in human brain associated with chronic degenerative disease. These lesions included diffuse and consolidated amyloid deposits, cerebral amyloid angiopathy, neurofibrillary tangles, neuropil threads and complement activated oligodendroglia. The staining for AP generally paralleled that for complement proteins C4d and C3d, suggesting that AP may serve as an adjuvant for phagocytosis6.
Human Amyloid P Component- An Elastase Inhibitor: Amyloid deposits almost invariably contain a pentagonal-shaped protein (a so-called pentraxin), termed AP, in close opposition to the amyloid fibrils. AP is also detected alongside normal dust elastin fibres in skin and basement membrane. In a study, 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°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 55% 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 proteolysis7.
References
1. Schneider HM, Loos M (1978). Amyloid P-component--a special type of collagen? Virchows Arch. B Cell Pathol., 29(3):225-228.
2. Prelli F, Pras M, Frangione B (1985). The primary structure of human tissue amyloid P component from a patient with primary idiopathic amyloidosis. J Biol Chem., 260(24):12895-12898.
3. Pepys MB, Baltz M, Gomer K, Davies AJ, Doenhoff M. (1979). Serum amyloid P-component is an acute phase reactant in the mouse. Nature, 278(5701):259-261.
4. Baltz ML, Gomer K, Davies AJ, Evans DJ, Klaus GG, Pepys MB (1980) Differences in the acute phase responses of serum amyloid P-component (SAP) and C3 to injections of casein or bovine serum albumin in amyloid-susceptible and resistant mouse strains. Clin. exp. Immunol., 39(2):355-360.
5. Holck M, Husby G, Sletten K, Natvig JB (1979). The amyloid P-component (Protein AP): an integral part of the amyloid substance? Scand. J. Immunol., 10(1):55-60.
6. Akiyama H, Yamada T, Kawamata T, McGeer PL (1991). Association of amyloid P component with complement proteins in neurologically diseased brain tissue. Brain Res., 548(1-2):349-352.
7. Li JJ, Mc Adam KP (2006). Human Amyloid P Component: An Elastase Inhibitor. Scandinavian Journal of Immunology., 20(3):219-226.
