Skip to main content

C-reactive protein

An activator of innate immunity and a modulator of adaptive immunity

Abstract

C-reactive protein (CRP) is an acute-phase serum protein and a member of the pentraxin protein family. Its host defense functions predate the adaptive immune system by millions of years. Our current understanding of CRP interactions with complement and with Fcγ receptors (FcγR) have led to an increased appreciation of the regulatory role of CRP in inflammation and autoimmunity. This review outlines the role of CRP in infection, inflammation, and autoimmune disease. We provide a discription of recent studies, which suggest that CRP acts through FcγR to reduce inflammation and protect from certain autoimmune diseases. A general description of the proposed function of CRP is provided as a framework for future in vestigation.

This is a preview of subscription content, access via your institution.

References

  1. Tillett WS, Francis T, Jr.: Serological reactions in pneumonia with a non-protein fraction of pneumococcus. J Exp Med 1930;52:561–571.

    CAS  PubMed  Google Scholar 

  2. Thompson D, Pepys MB, Wood SP: The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure 1999;7:169–177.

    PubMed  CAS  Google Scholar 

  3. Shrive AK, Cheetham GM, Holden D, Myles DA, Turnell WG, Volanakis JE, et al.: Three dimensional structure of human C-reactive protein. Nature Struct Biol 1996;3:346–354.

    PubMed  CAS  Google Scholar 

  4. Osmand AP, Friedenson B, Gewurz H, Painter RH, Hofmann T, Shelton E: Characteriation of C-reactive protein and the complement subcomponent Clt as homologous proteins displaying cyclic pentameric symmetry (pentraxins). Proc Natl Acad Sci USA 1977;74:739–743.

    PubMed  CAS  Google Scholar 

  5. 5.Agrawal A, Shrive AK, Greenhough TJ, Volanakis JE: Topology and structure of the Clq-binding site on C-reactive protein. J Immunol 2001;166:3998–4004.

    PubMed  CAS  Google Scholar 

  6. Agrawal A, Volanakis JE: Probing the Clq-binding site on human C-reactive protein by site-directed mutagenesis J Immunol 1994;152:5404–5410.

    PubMed  CAS  Google Scholar 

  7. Marnell LL, Mold C, Volzer MA, Burlingame RW, Du Clos TW: C-reactive protein binds to FcγRI in transfected COS cells. J Immunol 1995;155:2185–2193.

    PubMed  CAS  Google Scholar 

  8. Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, et al.: The crystal structure of the globular head of complement protein Clq provides a basis for its versatile recognition properties. J Biol Chem 2003;278:46974–46982.

    PubMed  CAS  Google Scholar 

  9. Hurlimann J, Thorbecke GJ, Hochwald GM: The liver as the site of C-reactive protein formation. J Exp Med 1966;123:365–378.

    PubMed  CAS  Google Scholar 

  10. Weinhold B, Rüther U: Interleukin-6-dependent and independent regulation of the human C-reactive protein gene. Biochem J 1997;327:425–429.

    PubMed  CAS  Google Scholar 

  11. Mackiewicz A, Speroff T, Ganapathi MK, Kushner I: Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines. J Immunol 1991;146:3032–3037.

    PubMed  CAS  Google Scholar 

  12. Li S-P, Liu T-Y, Goldman ND: cis-Acting elements responsible for interleukin-6 inducible C-reactive protein expression. J Biol Chem 1990;265:4136–4142.

    PubMed  CAS  Google Scholar 

  13. Macintyre S, Samols D, Dailey P: Two carboxylesterases bind C-reactive protein within the endoplasmic reticulum and regulate its secretion during the acute phase response. J Biol Chem 1994;269:24496–24503.

    PubMed  CAS  Google Scholar 

  14. Macintyre SS, Kushner I, Samols D: Secretion of C-reactive protein becomes more efficient during the course of the acute phase response. J Biol Chem 1985;260:4169–4173.

    PubMed  CAS  Google Scholar 

  15. Kushner I, Broder MI, Karp D: Control of the acute phase response. Serum C-reactive protein kinetics after acute myocardial infarction. J Clin Invest 1978;61:235.

    PubMed  CAS  Google Scholar 

  16. Pepys MB, Lanham JG, De Beer FC: C-reactive protein in SLE. Clin Rheum Dis 1982;8:91–103.

    PubMed  CAS  Google Scholar 

  17. Martin MFR, Dieppe PA, whicher J, Bell AM: Defective acute phase responses in scleroderma. Ann Rheum Dis 1988;194.

  18. Becker GJ, Waldburger M, Hughes GR, Pepys MB: Value of serum C-reactive protein measurement in the investigation of fever in systemic lupus erythematosus. Ann Rheum Dis 1980;39:50–52.

    PubMed  CAS  Google Scholar 

  19. Nakahara C, Kanemoto K, Saito N, Oyake Y, Kamoda T, Nagata M, Matsui A: C-reactive protein frequently localizes in the kidney in glomerular diseases. Clin Nephrol 2001;55:365–370.

    PubMed  CAS  Google Scholar 

  20. Baidoshvili A, Nijmeijer R, Lagrand WK, Hack CE, Niessen HW: Localisation of C reactive protein in infarcted tissue sites of multiple organs during sepsis. J Clin Path 2002;55:152–153.

    PubMed  CAS  Google Scholar 

  21. Zuniga R, Markowitz GS, Arkachaisri T, Imperatore EA, D'Agati VD, Salmon JE: Identification of IgG subclasses and C-reactive protein in lupus nephritis: The relationship between the composition of immune deposits and Fc gamma receptor type IIA alleles. Arthritis Rheum 2003;48:460–470.

    PubMed  CAS  Google Scholar 

  22. Kushner I, Rakita L, Kaplan MH: Studies of acutephase protein. II. Localization of Cxreactive protein in heart in induced myocardial infarction in rabbits. J Clin Invest 1963;42:286–292.

    PubMed  CAS  Google Scholar 

  23. Gitlin JD, Gitlin JI, Gitlin D: Localization of C-reactive protein in synovium of patients with rheumatoid arthritis. Arthritis Rheum 1977;20:1491–1499.

    PubMed  CAS  Google Scholar 

  24. Du Clos TW, Mold C, Paterson PY, Alroy J, Gewurz H: Localization of C-reactive protein in inflammatory lesions of experimental allergic encephalomyelitis. Clin Exp Immunol 1981;43:565–573.

    PubMed  Google Scholar 

  25. Russell AI, Cunninghame Graham DS, Shepherd C, Roberton CA, Whittaker J, Meeks J, et al.: Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. Hum Mol Genet 2004;13:137–147.

    PubMed  CAS  Google Scholar 

  26. Parish WE: Studies on vasculitis. I. Immunoglobulins, 1C, C-reactive protein, and bacterial antigens in cutaneous vasculitis lesions. Clin Allergy 1971;1:97–109.

    PubMed  CAS  Google Scholar 

  27. Kushner I, Kaplan MH: Studies of acute phase protein. I. An immunohistochemical method for the localization of Cx-reactive protein in rabbits: association with necrosis in inflammatory lesions. J Exp Med 1961;114:961–973.

    PubMed  CAS  Google Scholar 

  28. Szalai AJ, McCrory MA, Cooper GS, Wu J, Kimberly RP: Association between baseline levels of C-reactive protein (CRP) and a dinucleotide repeat polymorphism in the intron of the CRP gene. Genes Immun 2002;3:14–19.

    PubMed  CAS  Google Scholar 

  29. Vickers MA, Green FR, Terry C, Mayosi BM, Julier C, Lathrop M, et al.: Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 2002;53:1029–1034.

    PubMed  CAS  Google Scholar 

  30. Ferrari SL, Ahn-Luong L, Garnero P, Humphries SE, Greenspan SL: Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrinol Metab 2003;88:255–259.

    PubMed  CAS  Google Scholar 

  31. Berger P, McConnell JP, Nunn M, Kornman KS, Sorrell J, Stephenson K, Duff GW: C-reactive protein levels are influenced by common IL-1 gene variations. Cytokine 2002;17:171–174.

    PubMed  CAS  Google Scholar 

  32. Stein MP, Edberg JC, Kimberly RP, Mangan EK, Bharadwaj D, Mold C, Du Clos TW: C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele specific. J Clin Invest 2000;105:369–376.

    PubMed  CAS  Article  Google Scholar 

  33. Weiser JN, Pan N, McGowan KL, Musher D, Martin A, Richards J: Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. J Exp Med 1998;187:631–640.

    PubMed  CAS  Google Scholar 

  34. Narkates AJ, Volanakis JE: C-reactive protein binding specificities: artificial and natural phospholipid bilayers. Ann NY Acad Sci 1982;389:172–181.

    PubMed  CAS  Google Scholar 

  35. Li YP, Mold C, Du Clos TW: Sublytic complement attack exposes C-reactive protein binding sites on cell membranes. J Immunol 1994;152:2995–3005.

    PubMed  CAS  Google Scholar 

  36. Vigo C: Effect of C-reactive protein on platelet-activating factor-induced platelet aggregation and membrane stabilization. J Biol Chem 1985;260:3418–3422.

    PubMed  CAS  Google Scholar 

  37. Kilpatrick JM, Virella G: Inhibition of platelet activating factor by rabbit C-reactive protein. Clin Immunol Immunopathol 1985;37:276–281.

    PubMed  CAS  Google Scholar 

  38. Filep JG, Herman F, Kelemen E, Foldes-Filep E: C-reactive protein inhibits binding of platelet-activating factor to human platelets. Thrombosis Res 1991;61:411–421.

    CAS  Google Scholar 

  39. Du Clos TW: The interaction of C-reactive protein and serum amyloid P component with nuclear antigens. Mol Biol Rep 1997;23:253–260.

    Google Scholar 

  40. Robey FA, Jones KD, Tanaka T, Liu T-Y: Binding of C-reactive protein to chromatin and nucleosome core particles. A possible physiological role of C-reactive protein. J Biol Chem 1984;259:7311–7316.

    PubMed  CAS  Google Scholar 

  41. Du Clos TW: C-reactive protein reacts with the U1 small nuclear ribonucleoprotein. J Immunol 1989; 143:2553–2559.

    PubMed  Google Scholar 

  42. Pepys MB, Booth SE, Tennent GA, Butler PJG, Williams DG: Binding of pentraxins to different nuclear structures: C-reactive protein binds to small nuclear ribonucleoprotein particles, serum amyloid P component binds to chromatin and nucleoli. Clin Exp Immunol 1994;97:152–157.

    PubMed  CAS  Article  Google Scholar 

  43. Du Clos TW, Zlock L, Marnell LL: Definition of a C-reactive protein binding determinant on histones. J Biol Chem 1991;266:2167–2171.

    PubMed  Google Scholar 

  44. Jewell WS, Marnell LL, Rokeach LA, Du Clos TW: C-reactive protein binding to the Sm-D protein of snRNPs. Identification of a short polypeptide binding region. Mol Immunol 1993;30:701–708.

    PubMed  CAS  Google Scholar 

  45. Riemekasten M, Trebeljahr K, Hausdorf H, Burmester H: A novel epitope on the C-terminus of SmD1 is recognized by the majority of sera from patients with systemic lupus erythematosus. J Clin Invest 1998;102:754–763.

    PubMed  CAS  Google Scholar 

  46. Riemekasten G, Kawald A, Weiss C, Meine A, Marell J, Klein R, et al.: Strong acceleration of murine lupus by injection of the SmD183-119 peptide. Arthritis Rheum 2001;44:2435–2445.

    PubMed  CAS  Google Scholar 

  47. Kim SJ, Gershov D, Ma X, Brot N, Elkon KB: Opsonization of apoptotic cells and its effect on macrophage and T cell immune responses. Ann NY Acad Sci 2003;987:68–78.

    PubMed  CAS  Google Scholar 

  48. Mold C, Nakayama S, Holzer TJ, Gewurz H, Du Clos TW: C-reactive protein is protective against Streptococcus pneumoniae infection in mice. J Exp Med 1981;154:1703–1708.

    PubMed  CAS  Google Scholar 

  49. Mortensen RF, Osmand AP, Lint TF, Gewurz H: Interaction of C-reactive protein with lymphocytes and monocytes: Complement-dependent adherence and phagocytosis. J Immunol 1976;117:774–781.

    PubMed  CAS  Google Scholar 

  50. Nakayama S, Mold C, Gewurz H, Du Clos TW: Opsonic properties of C-reactive protein in vivo. J Immunol 1982; 128:2435–2438.

    PubMed  CAS  Google Scholar 

  51. Mold C, Rodic-Polic B, Du Clos TW: Protection from Streptococcus pneumoniae infection by C-reactive protein and natural antibody requires complement but not Fc gamma receptors. J Immunol 2002;168:6375–6381.

    PubMed  CAS  Google Scholar 

  52. Szalai AJ: The antimicrobial activity of C-reactive protein. Microbes Infect 2002;4:201–205.

    PubMed  CAS  Google Scholar 

  53. Berman S, Gewurz H, Mold C: Binding of C-reactive protein to nucleated cells leads to complement activation without cytolysis. J Immunol 1986;136:1354–1359.

    PubMed  CAS  Google Scholar 

  54. Mold C, Gewurz H, Du Clos TW: Regulation of complement by C-reactive protein. Immunopharm 1999; 42:23–30.

    CAS  Google Scholar 

  55. Giannakis E, Jokiranta TS, Male DA, Ranganathan S, Ormsby RJ, Fischetti VA, et al.: A common site within factor H SCR 7 responsible for binding heparin, C-reactive protein and streptococcal M protein. Eur J Immunol 2003;33:962–969.

    PubMed  CAS  Google Scholar 

  56. Wolbink GJ, Brouwer MV, Buysmann S, ten Berge IJM, Hack EC: CRP-mediated activation of complement in vivo. J Immunol 1996;157:473–479.

    PubMed  CAS  Google Scholar 

  57. Lagrand WK, Niessen HWM, Wolbink G-J, Jaspars LH, Visser CA, Verheugt FWA, et al.: C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation 1997;95:97–103.

    PubMed  CAS  Google Scholar 

  58. Ganrot PO, Kindmark C-O. C-reactive protein—a phagocytosis-promoting factor. Scand J Lab Clin Invest 1969;24:215–219.

    CAS  Google Scholar 

  59. Mortensen RF, Duszkiewicz JA: Mediation of CRP-dependent phagocytosis through mouse macrophage Fc-receptors. J Immunol 1977;119:1611–1616.

    PubMed  CAS  Google Scholar 

  60. Kilpatrick JM, Volanakis JE: Opsonic properties of C-reactive protein. Stimulation by phorbol myristate acetate enables human neutrophils to phagocytize C-reactive protein-coated cells. J Immunol 1985;134:3364–3370.

    PubMed  CAS  Google Scholar 

  61. Nakagomi A, Freedman SB, Geczy CL: Interferongamma and lipopolysaccharide potentiate monocyte tissue factor induction by C-reactive protein: relationship with age, sex, and hormone replacement treatment. Circulation 2000;101:1785–1791.

    PubMed  CAS  Google Scholar 

  62. Pue CA, Mortensen RF, Marsh CB, Pope HA, Wewers MD: Acute phase levels of C-reactive protein enhance IL-1b and IL-1ra production by human blood monocytes but inhibit IL-1b and IL-1ra production by alveolar macrophages. J Immunol 1996;156:1594–1600.

    PubMed  CAS  Google Scholar 

  63. Tilg H, Vannier E, Vachino G, Dinarello CA, Mier JW: Antiinflammatory properties of hepatic acute phase proteins: Preferential induction of Interleukin 1 (IL-1) receptor antagonist over IL-1β synthesis by human peripheral blood mononuclear cells. J Exp Med 1993;178:1629–1636.

    PubMed  CAS  Google Scholar 

  64. Zeller JM, Kubak BM, Gewurz H: Binding sites for C-reactive protein on human monocytes are distinct from IgG Fc receptors. Immunol 1989;67:51–55.

    CAS  Google Scholar 

  65. Muller H, Fehr J: Binding of C-reactive protein to human polymorphonuclear leukocytes: evidence for association of binding sites with Fc receptors. J Immunol 1986;136:2202–2207.

    PubMed  CAS  Google Scholar 

  66. Zeller JM, Landay AL, Lint TF, Gewurz H: Enhancement of human peripheral blood monocyte burst activity by aggregated C-reactive protein. J Leuk Biol 1986;40:769.

    CAS  Google Scholar 

  67. Cosio G, Douglas SD, Michael AF: The human FcR: effects of pronase on soluble immune complex binding by polymorphonuclear leucocytes, monocytes and pulmonary macrophages. Immunol 1982;46:395–400.

    CAS  Google Scholar 

  68. Debets JMH, van de Winkel JGJ, Ceuppens JL, Dieteren IEM, Buurman WA: Cross-linking of both Fc gamma RI and Fc gamma RII induces secretion of tumor necrosis factor by human monocytes, requiring high affinity Fc-Fc gamma R interactions: functional activation of Fc gamma RII by treatment with proteases or neuraminidase. J Immunol 1990;144:1304–1310.

    PubMed  CAS  Google Scholar 

  69. van de Winkel JGJ, van Ommen R, Huizinga TWJ, de Raad MAHVM, Tuijnman WB, Groenen PJTA, et al.: Proteolysis induces increased binding affinity of the monocyte type II FcR for human IgG. J Immunol 1989;143:571–578.

    PubMed  Google Scholar 

  70. Crowell RE, Du Clos TW, Montoya G, Heaphy E, Mold C: C-reactive protein receptors on the human monocytic cell line U-937. Evidence for additional binding to FcγRI. J Immunol 1991;147:3445–3451.

    PubMed  CAS  Google Scholar 

  71. Bodman-Smith KB, Melendez AJ, Campbell I, Harrison PT, Allen JM, Raynes JG: C-reactive proteinmediated phagocytosis and phospholipase D signalling through the high-affinity receptor for immunoglobulin G (FcgammaRI). Immunol 2002;107:252–260.

    CAS  Google Scholar 

  72. Szabo G, Miller-Graziano CL, Wu JY, Takayama T, Kodys K: Differential tumor necrosis factor production by human monocyte subsets. J Leuk Biol 1990; 47:206–216.

    CAS  Google Scholar 

  73. Bharadwaj D, Stein MP, Volzer M, Mold C, Du Clos TW: The major receptor for C-reactive protein on leukocytes is FcγRII. J Exp Med 1999;190:585–590.

    PubMed  CAS  Google Scholar 

  74. Bharadwaj D, Mold C, Markham E, Du Clos TW: Serum amyloid P component binds to Fcgamma receptors and opsonizes particles for phagocytosis. J Immunol 2001;166:6735–6741.

    PubMed  CAS  Google Scholar 

  75. Chi M, Tridandapani S, Zhong W, Coggeshall KM, Mortensen RF: C-reactive protein induces signaling through Fc gamma RIIa on HL-60 granulocytes. J Immunol 2002;168:1413–1418.

    PubMed  CAS  Google Scholar 

  76. Schiff DE, Rae J, Martin TR, Davis BH, Curnutte JT: Increased phagocyte FcgammaRI expression and improved Fcgamma-receptor-mediated phagocytosis after in vivo recombinant human interferon-gamma treatment of normal human subjects. Blood 1997;90:3187–3194.

    PubMed  CAS  Google Scholar 

  77. Ballou SP, Lozanski G: Induction of inflammatory cytokine release from human monocytes by C-reactive protein. Cytokine 1992;4:361–368.

    PubMed  CAS  Google Scholar 

  78. Galve-de Rochemonteix B, Wiktorowicz K, Kushner I, Dayer JM: C-reactive protein increases production of IL-l alpha, IL-1 beta, and TNF-alpha, and expression of mRNA by human alveolar macrophages. J Leuk Biol 1993;53:439–445.

    CAS  Google Scholar 

  79. Arend WP, Smith MF, Janson RW, Joslin FG: IL-1 receptor antagonist and IL-1 beta production in human monocytes are regulated differently. J Immunol 1991;147:1530–1536.

    PubMed  CAS  Google Scholar 

  80. Mold C, Rodriguez W, Rodic-Polic B, Du Clos TW: C-reactive protein mediates protection from lipopolysaccharide through interactions with Fc gamma R. J Immunol 2002;169:7019–7025.

    PubMed  CAS  Google Scholar 

  81. Stein MP, Mold C, Du Clos TW: C-reactive protein binding to murine leukocytes requires Fcγ receptors. J Immunol 2000;164:1514–1520.

    PubMed  CAS  Google Scholar 

  82. Sylvestre DL, Ravetch JV: A dominant role for mast cell Fc receptors in the Arthus reaction. Immunity 1996;5:387–390.

    PubMed  CAS  Google Scholar 

  83. Mold C, Gresham HD, Du Clos TW: Serum amyloid P component (SAP) and C-reactive protein (CRP) mediate phagocytosis through murine Fcγ receptors. J Immunol 2001;166:1200–1205.

    PubMed  CAS  Google Scholar 

  84. Sutterwala FS, Noel GJ, Salgame P, Mosser DM: Reversal of proinflammatory responses by ligating the macrophage Fcγ receptor type I. J Exp Med 1998;188:217–222.

    PubMed  CAS  Google Scholar 

  85. Ravetch JV, Lanier LL: Immune inhibitory receptors. Science 2000;290:84–89.

    PubMed  CAS  Google Scholar 

  86. Takai T, Ono M, Hikida M, Ohmori H, Ravetch JV: Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice. Nature 1995;379:346–349.

    Google Scholar 

  87. Clynes R, Maizes JS, Guinamard R, Ono M, Takai T, Ravetch JV: Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors. J Exp Med 1999;189:179–185.

    PubMed  CAS  Google Scholar 

  88. Szalai AJ, VanCott JL, McGhee JR, Volanakis JE, Benjamin WH, Jr.: Human C-reactive protein is protective against fatal Salmonella enterica Serovar Typhimurium infection in transgenic mice. Infect Immun 2000;68:5652–5656.

    PubMed  CAS  Google Scholar 

  89. Colina J, Shen Y, Snapper CM: Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein-and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms. J Exp Med 2002;195:1–13.

    Google Scholar 

  90. Szalai AJ, Briles DE, Volanakis JE: Human C-reactive protein is protective against fatal Streptococcus pneumoniae infection in transgenic mice. J Immunol 1995;155:2557–2563.

    PubMed  CAS  Google Scholar 

  91. Lysenko E, Richards JC, Cox AD, Stewart A, Martin A, Kapoor M, Weiser JN: The position of phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae affects binding and sensitivity to C-reactive protein mediated killing. Mol Immunol 2000;35:234–235.

    CAS  Google Scholar 

  92. Szalai AJ, Briles DE, Volanakis JE: Role of complement in C-reactive protein-mediated protection of mice from Streptococcus pneumoniae. Infect Immun 1996;64:4850–4853.

    PubMed  CAS  Google Scholar 

  93. Saeland E, Vidarsson G, Leusen JH, Van Garderen E, Nahm MH, Vile-Weekhout H, et al.: Central role of complement in passive protection by human IgG1 and IgG2 anti-pneumococcal antibodies in mice. J Immunol 2003;170:6158–6164.

    PubMed  CAS  Google Scholar 

  94. Xia D, Samols D: Transgenic mice expressing rabbit C-reactive protein are resistant to endotoxemia. Proc Natl Acad Sci USA 1997;94:2575–2580.

    PubMed  CAS  Google Scholar 

  95. Chae MR, Park BH, Kim JS, Rho JW, Kim HR: Protective effect of C-reactive protein against the lethality induced by Vibrio vulnificus lipopolysaccharide. Microbiol Immunol 2000;44:335–340.

    PubMed  CAS  Google Scholar 

  96. Noursadeghi M, Bickerstaff MC, Gallimore JR, Herbert J, Cohen J, Pepys MB: Role of serum amyloid P component in bacterial infection: protection of the host or protection of the pathogen. Proc Natl Acad USA 2000;97:14584–14589.

    CAS  Google Scholar 

  97. Heuertz RM, Samols D, Webster RO: Transgenic mice expressing plasma rabbit C-reactive protein exhibit diminished vascular permeability and neutrophil infiltration in C5a-induced alveolitis. FASEB J 1994;8:A1064.

    Google Scholar 

  98. Heuertz RM, Dongyuan X, Samols D, Webster RO: Inhibition of C5a des Arg-induced neutrophil alveolitis in transgenic mice expressing C-reactive protein. Am J Physiol 1994;266:L649-L654.

    PubMed  CAS  Google Scholar 

  99. Kew RM, Hyers TM, Webster RO: Human C-reactive protein inhibits neutrophil chemotaxis in vitro: Possible implications for the adult respiratory distress syndrome. J Lab Clin Med 1990;115:339–345.

    PubMed  CAS  Google Scholar 

  100. Gerard C, Bruyns C, Marchant A, Abramowicz D, Vandenabeele P, Delvaux A, et al. Interleukin 10 reduces the release of Tumor Necrosis Factor and prevents lethality in experimental endotoxemia. J Exp Med 1993;177:547–550.

    PubMed  CAS  Google Scholar 

  101. Du Clos TW, Zlock L, Hicks PS, Mold C: Decreased autoantibody levels and enhanced survival of (NZB X NZW) F1 mice treated with C-reactive protein. Clin Immunol Immunopath 1994;70:22–27.

    Google Scholar 

  102. Szalai AJ, Weaver CT, McCrory MA, van Ginkel FW, Reiman RM, Kearney JF, et al.: Delayed lupus onset in (NZBxNZW)F1 mice expressing a human C-reactive protein transgene. Arthritis Rheum 2003;48:1602–1611.

    PubMed  CAS  Google Scholar 

  103. Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG: A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997;389:737–742.

    PubMed  CAS  Google Scholar 

  104. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH: Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973–979.

    PubMed  CAS  Google Scholar 

  105. Ridker P, Buring J, Shih J, Matiaws M, Hennekens C: Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998;98:731–733.

    PubMed  CAS  Google Scholar 

  106. Griselli M, Herbert J, Hutchinson WL, Taylor KM, Sahail M, Drausz T, Pepys MB: C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 1999; 190:1733–1739.

    PubMed  CAS  Google Scholar 

  107. Nagpurkar A, Mookerjea S: A novel phosphorylcholine-binding protein from rat serum and its effect on heparin-lipoprotein complex formation in the presence of calcium. J Biol Chem 1981;256:7440–7446.

    PubMed  CAS  Google Scholar 

  108. Diaz Padilla N, Bleeker WK, Lubbers Y, Rigter GM, Van Mierlo GJ, Daha MR, Hack CE: Rat C-reactive protein activates the autologous complement system. Immunol 2003;109:564–571.

    Google Scholar 

  109. Cermak J, Key N, Bach R, Balla J, Jacob H, Vercellotti G: C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993;82:513–520.

    PubMed  CAS  Google Scholar 

  110. Zhou P, Thomassen MJ, Pettay J, Deodhar SD, Barna BP: Human monocytes produce monocyte chemoattractant protein 1 (MCP-1) in response to a synthetic peptide derived from C-reactive protein. Clin Immunol Immunopathol 1995;74:84–88.

    PubMed  CAS  Google Scholar 

  111. Pasceri V, Cheng JS, Willerson JT, Yeh ET, Chang J: Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001;103:2531–2534.

    PubMed  CAS  Google Scholar 

  112. Danenberg HD, Szalai AJ, Swaminathan RV, Peng L, Chen Z, Seifert P, et al.: Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice C-reactive protein, lipoprotein(a), homocysteine, and male sex contribute to carotid atherosclerosis in peritoneal dialysis patients. Circulation 2003;108:512–515.

    PubMed  CAS  Google Scholar 

  113. Rodriguez W, Mold C, Katavanovski M, Hutt J, Marnell LL, DuClos TW: C-reactive protein reverses on going proteinuria in autoimmune mice. Arthritis Rheum 2004; in press.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Du Clos, T.W., Mold, C. C-reactive protein. Immunol Res 30, 261–277 (2004). https://doi.org/10.1385/IR:30:3:261

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/IR:30:3:261

Key words

  • C-reactive protein
  • Acute-phase response
  • Pentraxins
  • Autoimmune mice
  • Inflammation
  • Fc receptors
  • LPS
  • SLE
  • Complement