Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene

Botto, Marina; Hawkins, Philip N.; Bickerstaff, Maria C. M.; Herbert, Jeff; Bygrave, Anne E.; McBride, Alan G.; Hutchinson, Winston L.; Tennent, Glenys A.; Walport, Mark J.; Pepys, Mark B.

doi:10.1038/nm0897-855

Cited by 230 publications

(165 citation statements)

References 34 publications

Supporting

Mentioning

157

Contrasting

Unclassified

Order By: Relevance

“…Therefore, SAP is seemingly not necessary for the initiation of amyloid ®brillogenesis, but may stabilize and protect mature ®brils [15]. The ®nding that development of amyloidosis in SAP-de®cient mice was delayed compared to in normal mice [16,17] is compatible with the interpretation of our data.…”

Section: Discussionsupporting

confidence: 87%

Localization of Human Serum Amyloid P Component and Heparan Sulfate Proteoglycan in In Vitro‐Formed Aβ Fibrils

Nielsen¹,

Nybo

Junker

et al. 2000

Scand J Immunol

View full text Add to dashboard Cite

Ultrastructural studies of the localization of serum amyloid P component (SAP) in amyloid ®brils have given divergent results. We here report for the ®rst time that electron microscopy of SAP coincubated with Ab 1±42 peptides or with mature Ab 1±42 ®brils, revealed SAP molecules coating the surface of the mature ®brils and that proto®brils of Ab 1±42 did not bind SAP. Also when incubated with extracted amyloid light chain (AL)-®brils the SAP molecules aligned on the ®bril surface. Heparan sulfate proteoglycan bound to the surface of the Ab ®brils with a spacing of about 50 nm. We conclude that SAP does not bind to proto®brils but to the surface of mature Ab ®brils and that it may stabilize and protect the ®brils.

show abstract

Section: Discussionsupporting

confidence: 87%

Localization of Human Serum Amyloid P Component and Heparan Sulfate Proteoglycan in In Vitro‐Formed Aβ Fibrils

Nielsen¹,

Nybo

Junker

et al. 2000

Scand J Immunol

View full text Add to dashboard Cite

show abstract

“…A proposal has been made that all amyloid deposits are being degraded continuously [110], possibly by removal by macrophages, and that accumulation of deposits could result from a deficiency in the factors responsible for degradation and/or turnover [111]. Although IAPP fibrils have been detected in pancreatic macrophages [112], amyloid deposition is not associated with increased macrophage density [113].…”

Section: Iapp Concentrationmentioning

confidence: 99%

“…Although IAPP fibrils have been detected in pancreatic macrophages [112], amyloid deposition is not associated with increased macrophage density [113]. The many amyloid-associated factors including the amyloid P component [111] and glycosaminoglycans have been proposed to prevent recognition of deposits for phagocytosis by macrophages and thus reduce clearance of deposits [111].…”

Section: Iapp Concentrationmentioning

confidence: 99%

“…5) suggesting that the time course of synthetic fibril-induced toxicity is more rapid than that induced by biosynthetic hIAPP in vitro or in vivo. One suggestion is that the amyloidassociated proteins, SAP, ApoE, and glycosaminoglycans can act as protective factors in biological systems by reducing the impact of oligomers or fibrils on cell viability as well as reducing recognition for degradation or clearance of misfolded peptide [111]. However, rather than causing immediate cell death, small fibril accumulations could affect function; the betacell membranes adjacent to biosynthetic deposits in vivo (Fig.…”

Section: Fibril-induced Cell Deathmentioning

confidence: 99%

See 1 more Smart Citation

Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes?

2004

View full text Add to dashboard Cite

The role of islet amyloidosis in the onset and progression of Type 2 diabetes remains obscure. Islet amyloid polypeptide is a 37 amino-acid, beta-cell peptide which is co-stored and co-released with insulin. Human islet amyloid polypeptide refolds to a β-conformation and oligomerises to form insoluble fibrils; proline substitutions in rodent islet amyloid polypeptide prevent this molecular transition. Pro-islet amyloid polypeptide (67 amino acids in man) is processed in secretory granules. Refolding of islet amyloid polypeptide may be prevented by intragranular heterodimer formation with insulin (but not proinsulin). Diabetes-associated abnormal proinsulin processing could contribute to de-stabilisation of granular islet amyloid polypeptide. Increased pro-islet amyloid polypeptide secretion as a consequence of islet dysfunction could promote fibrillogenesis; the propeptide forms fibrils and binds to basement membrane glycosamino-glycans. Islet amyloid polypeptide gene polymorphisms are not universally associated with Type 2 diabetes. Transgenic mice expressing human islet amyloid polypeptide gene have increased islet amyloid polypeptide concentrations but develop islet amyloid only against a background of obesity and/or high fat diet. In transgenic mice, obese monkeys and cats, initially small perivascular deposits progressively increase to occupy 80% islet mass; the severity of amyloidosis in animal models is related to the onset of hyperglycaemia, suggesting that islet amyloid and the associated destruction of islet cells cause diabetes. In human diabetes, islet amyloid can affect less than 1% or up to 80% of islets indicating that islet amyloidosis largely results from diabetes-related pathologies and is not an aetiological factor for hyperglycaemia. However, the associated progressive betacell destruction leads to severe islet dysfunction and insulin requirement. [Diabetologia (2004) 47:157-169]

show abstract

“…No CRP-knockout mouse has been described, but the SAP-knockout mouse is fertile, healthy, and has a normal life span (6). The main phenotypic features of SAP-deficient mice are as follows: 1) impaired innate immunity against certain pathogens to which SAP does not bind and enhanced resistance to bacterial pathogens to which SAP binds, reflecting the fact that SAP is a potent antiopsonin (7), and 2) reduced and retarded deposition of AA amyloid induced by chronic inflammation (6).…”

mentioning

confidence: 99%

Normal circulating serum amyloid P component concentration in systemic sclerosis

Tennent¹,

Dziadzio²,

Triantafillidou³

et al. 2007

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. The observation of reduced circulating concentrations of the constitutive plasma pentraxin protein, serum amyloid P component (SAP), in serum samples obtained from a small number of patients with systemic sclerosis (SSc) has been reported as confirmation of an antifibrotic role of this protein. Because neither sustained SAP depletion in humans nor SAP deficiency in mice is associated with fibrosis, we sought to establish rigorously the serum SAP concentration in well-characterized patients with SSc.Methods. Serum concentrations of SAP were measured by electroimmunoassay in a cross-sectional cohort of 20 patients with diffuse cutaneous SSc and 12 patients with limited cutaneous SSc, and in a separate 12-month longitudinal cohort of 13 patients with diffuse disease and 37 patients with limited disease. The extent and severity of disease were characterized in detail at the time of serum sampling. Serum concentrations of the classic acute-phase reactants, C-reactive protein and serum amyloid A protein, were measured by immunonephelometric assays.Results. SAP values were entirely within the normal range, regardless of the extent and severity of disease, apart from a very few isolated raised values associated with acute intercurrent complications causing major acute-phase responses.Conclusion. We observed no reduced circulating concentrations of SAP in patients with SSc, nor any evidence of an association between SAP levels and the extent or severity of fibrosis.

show abstract

Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene

Cited by 230 publications

References 34 publications

Localization of Human Serum Amyloid P Component and Heparan Sulfate Proteoglycan in In Vitro‐Formed Aβ Fibrils

Localization of Human Serum Amyloid P Component and Heparan Sulfate Proteoglycan in In Vitro‐Formed Aβ Fibrils

Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes?

Normal circulating serum amyloid P component concentration in systemic sclerosis

Contact Info

Product

Resources

About