• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Oct 1994; 94(4): 1390–1396.
PMCID: PMC295264

The pentraxins, C-reactive protein and serum amyloid P component, are cleared and catabolized by hepatocytes in vivo.

Abstract

The cellular sites of clearance and degradation of the pentraxin plasma proteins, C-reactive protein, the classical acute phase reactant, and serum amyloid P component (SAP), a universal constituent of amyloid deposits, were sought using the ligand 125I-tyramine cellobiose (TC) which is substantially retained within the cells in which catabolism takes place. Pentraxins labeled with 125I-TC showed the same in vitro and in vivo ligand binding and the same in vivo plasma t1/2 as the directly iodinated proteins and the native unlabeled pentraxins, indicating that their mode of clearance was likely to be physiological. After intravenous injection into mice and rabbits of human C-reactive protein, human SAP, and mouse SAP, each labeled with 125I-TC, most of the radioactivity remaining in the body at 24 h was located in hepatocytes. None was detected in other liver cells, and only traces were present in other viscera; the rest was in the carcass, representing intact pentraxins in the blood and extravascular compartment, and escaped label which had not yet been excreted. Hepatocytes are thus the single major site of pentraxin clearance and catabolism in vivo. This is consistent with the observation that SAP that has localized to amyloid deposits persists there and is not degraded.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Pepys MB, Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv Immunol. 1983;34:141–212. [PubMed]
  • Emsley J, White HE, O'Hara BP, Oliva G, Srinivasan N, Tickle IJ, Blundell TL, Pepys MB, Wood SP. Structure of pentameric human serum amyloid P component. Nature. 1994 Jan 27;367(6461):338–345. [PubMed]
  • Pepys MB, Rademacher TW, Amatayakul-Chantler S, Williams P, Noble GE, Hutchinson WL, Hawkins PN, Nelson SR, Gallimore JR, Herbert J, et al. Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5602–5606. [PMC free article] [PubMed]
  • Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest. 1993 Apr;91(4):1351–1357. [PMC free article] [PubMed]
  • Hawkins PN, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component. N Engl J Med. 1990 Aug 23;323(8):508–513. [PubMed]
  • Baltz ML, Gomer K, Davies AJ, Evans DJ, Klaus GG, Pepys MB. 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. 1980 Feb;39(2):355–360. [PMC free article] [PubMed]
  • Snel FW, Niewold TA, Baltz ML, Hol PR, Van Ederen AM, Pepys MB, Gruys E. Experimental amyloidosis in the hamster: correlation between hamster female protein levels and amyloid deposition. Clin Exp Immunol. 1989 May;76(2):296–300. [PMC free article] [PubMed]
  • Coe JE, Ross MJ. Amyloidosis and female protein in the Syrian hamster. Concurrent regulation by sex hormones. J Exp Med. 1990 Apr 1;171(4):1257–1267. [PMC free article] [PubMed]
  • Kinoshita CM, Gewurz AT, Siegel JN, Ying SC, Hugli TE, Coe JE, Gupta RK, Huckman R, Gewurz H. A protease-sensitive site in the proposed Ca(2+)-binding region of human serum amyloid P component and other pentraxins. Protein Sci. 1992 Jun;1(6):700–709. [PMC free article] [PubMed]
  • Hawkins PN, Wootton R, Pepys MB. Metabolic studies of radioiodinated serum amyloid P component in normal subjects and patients with systemic amyloidosis. J Clin Invest. 1990 Dec;86(6):1862–1869. [PMC free article] [PubMed]
  • Hawkins PN, Richardson S, MacSweeney JE, King AD, Vigushin DM, Lavender JP, Pepys MB. Scintigraphic quantification and serial monitoring of human visceral amyloid deposits provide evidence for turnover and regression. Q J Med. 1993 Jun;86(6):365–374. [PubMed]
  • Hawkins PN, Richardson S, Vigushin DM, David J, Kelsey CR, Gray RE, Hall MA, Woo P, Lavender JP, Pepys MB. Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis. Arthritis Rheum. 1993 Jun;36(6):842–851. [PubMed]
  • Pittman RC, Carew TE, Glass CK, Green SR, Taylor CA, Jr, Attie AD. A radioiodinated, intracellularly trapped ligand for determining the sites of plasma protein degradation in vivo. Biochem J. 1983 Jun 15;212(3):791–800. [PMC free article] [PubMed]
  • JANIGAN DT. EXPERIMENTAL AMYLOIDOSIS: STUDIES WITH A MODIFIED CASEIN METHOD, CASEIN HYDROLYSATE AND GELATIN. Am J Pathol. 1965 Jul;47:159–171. [PMC free article] [PubMed]
  • De Beer FC, Pepys MB. Isolation of human C-reactive protein and serum amyloid P component. J Immunol Methods. 1982;50(1):17–31. [PubMed]
  • Pepys MB. Isolation of serum amyloid P-component (protein SAP) in the mouse. Immunology. 1979 Jul;37(3):637–641. [PMC free article] [PubMed]
  • Hawkins PN, Tennent GA, Woo P, Pepys MB. Studies in vivo and in vitro of serum amyloid P component in normals and in a patient with AA amyloidosis. Clin Exp Immunol. 1991 May;84(2):308–316. [PMC free article] [PubMed]
  • Reay P. Use of N-bromosuccinimide for the iodination of proteins for radioimmunoassay. Ann Clin Biochem. 1982 Mar;19(Pt 2):129–133. [PubMed]
  • Hawkins PN, Myers MJ, Epenetos AA, Caspi D, Pepys MB. Specific localization and imaging of amyloid deposits in vivo using 123I-labeled serum amyloid P component. J Exp Med. 1988 Mar 1;167(3):903–913. [PMC free article] [PubMed]
  • Baltz ML, Caspi D, Evans DJ, Rowe IF, Hind CR, Pepys MB. Circulating serum amyloid P component is the precursor of amyloid P component in tissue amyloid deposits. Clin Exp Immunol. 1986 Dec;66(3):691–700. [PMC free article] [PubMed]
  • Rowe IF, Baltz ML, Soutar AK, Pepys MB. In vivo turnover studies of C-reactive protein and lipoproteins in the rabbit. Clin Exp Immunol. 1984 Oct;58(1):245–252. [PMC free article] [PubMed]
  • Hu WL, Chindemi PA, Regoeczi E. In vivo behaviour of rat transferrin bearing a hybrid glycan and its interaction with macrophages. Biochem Cell Biol. 1992 Aug;70(8):636–642. [PubMed]
  • Goldberg IJ, Blaner WS, Vanni TM, Moukides M, Ramakrishnan R. Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys. J Clin Invest. 1990 Aug;86(2):463–473. [PMC free article] [PubMed]
  • Glass CK, Pittman RC, Keller GA, Steinberg D. Tissue sites of degradation of apoprotein A-I in the rat. J Biol Chem. 1983 Jun 10;258(11):7161–7167. [PubMed]
  • Moerlein SM, Dalal KB, Ebbe SN, Yano Y, Budinger TF. Residualizing and non-residualizing analogues of low-density lipoprotein as iodine-123 radiopharmaceuticals for imaging LDL catabolism. Int J Rad Appl Instrum B. 1988;15(2):141–149. [PubMed]
  • Gustafson S, Vahlquist C, Sjöblom L, Eklund A, Vahlquist A. Metabolism of very low density lipoproteins in rats with isotretinoin (13-cis retinoic acid)-induced hyperlipidemia. J Lipid Res. 1990 Feb;31(2):183–190. [PubMed]
  • Makover A, Moriwaki H, Ramakrishnan R, Saraiva MJ, Blaner WS, Goodman DS. Plasma transthyretin. Tissue sites of degradation and turnover in the rat. J Biol Chem. 1988 Jun 25;263(18):8598–8603. [PubMed]
  • Hysing J, Tolleshaug H. Quantitative aspects of the uptake and degradation of lysozyme in the rat kidney in vivo. Biochim Biophys Acta. 1986 Jun 16;887(1):42–50. [PubMed]
  • Kinoshita CM, Ying SC, Hugli TE, Siegel JN, Potempa LA, Jiang H, Houghten RA, Gewurz H. Elucidation of a protease-sensitive site involved in the binding of calcium to C-reactive protein. Biochemistry. 1989 Dec 12;28(25):9840–9848. [PubMed]
  • Hind CR, Collins PM, Caspi D, Baltz ML, Pepys MB. Specific chemical dissociation of fibrillar and non-fibrillar components of amyloid deposits. Lancet. 1984 Aug 18;2(8399):376–378. [PubMed]
  • Soutar AK, Hawkins PN, Vigushin DM, Tennent GA, Booth SE, Hutton T, Nguyen O, Totty NF, Feest TG, Hsuan JJ, et al. Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7389–7393. [PMC free article] [PubMed]
  • Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA, Soutar AK, Totty N, Nguyen O, Blake CC, Terry CJ, et al. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature. 1993 Apr 8;362(6420):553–557. [PubMed]
  • Pepys MB, Dash AC, Markham RE, Thomas HC, Williams BD, Petrie A. Comparative clinical study of protein SAP (amyloid P component) and C-reactive protein in serum. Clin Exp Immunol. 1978 Apr;32(1):119–124. [PMC free article] [PubMed]
  • Pepys MB, Baltz M, Gomer K, Davies AJ, Doenhoff M. Serum amyloid P-component is an acute-phase reactant in the mouse. Nature. 1979 Mar 15;278(5701):259–261. [PubMed]
  • Baltz ML, Dyck RF, Pepys MB. Studies of the in vivo synthesis and catabolism of serum amyloid P component (SAP) in the mouse. Clin Exp Immunol. 1985 Jan;59(1):235–242. [PMC free article] [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...