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Pentraxins in Innate Immunity: From C-Reactive Protein to the Long Pentraxin PTX3

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Abstract

Pentraxins are a family of multimeric pattern-recognition proteins highly conserved in evolution. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein and serum amyloid P-component are classic short pentraxins produced in the liver, whereas the prototype of the long pentraxin family is PTX3. Innate immunity cells and vascular cells produce PTX3 in response to proinflammatory signals and Toll-like receptor engagement. PTX3 interacts with several ligands, including growth factors, extracellular matrix components, and selected pathogens, playing a role in complement activation, facilitating pathogen recognition, and acting as a predecessor of antibodies. In addition, PTX3 is essential in female fertility acting on the assembly of the cumulus oophorus extracellular matrix. Thus, PTX3 is a multifunctional soluble pattern recognition receptor acting as a nonredundant component of the humoral arm of innate immunity and involved in tuning inflammation, in matrix deposition and female fertility. Evidence suggests that PTX3 is a useful new serological marker, rapidly reflecting tissue inflammation and damage under diverse clinical conditions.

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References

  1. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 2005;5:58–68.

    Article  PubMed  CAS  Google Scholar 

  2. Endo Y, Matsushita M, Fujita T. Role of ficolin in innate immunity and its molecular basis. Immunobiology 2007;212:371–9.

    Article  PubMed  CAS  Google Scholar 

  3. Bottazzi B, Garlanda C, Salvatori G, Jeannin P, Manfredi A, Mantovani A. Pentraxins as a key component of innate immunity. Curr Opin Immunol 2006;18:10–5.

    Article  PubMed  CAS  Google Scholar 

  4. Garlanda C, Bottazzi B, Bastone A, Mantovani A. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol 2005;23:337–66.

    Article  PubMed  CAS  Google Scholar 

  5. Agrawal A. CRP after 2004. Mol Immunol 2005;42:927–30.

    Article  PubMed  CAS  Google Scholar 

  6. Gewurz H, Zhang XH, Lint TF. Structure and function of the pentraxins. Curr Opin Immunol 1995;7:54–64.

    Article  PubMed  CAS  Google Scholar 

  7. Volanakis JE. Human C-reactive protein: expression, structure, and function. Mol Immunol 2001;38:189–97.

    Article  PubMed  CAS  Google Scholar 

  8. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 2003;111:1805–12.

    Article  PubMed  CAS  Google Scholar 

  9. Reid MS, Blobel CP. Apexin, an acrosomal pentaxin. J Biol Chem 1994;269:32615–20.

    PubMed  CAS  Google Scholar 

  10. Noland TD, Friday BB, Maulit MT, Gerton GL. The sperm acrosomal matrix contains a novel member of the pentaxin family of calcium-dependent binding proteins. J Biol Chem 1994;269:32607–14.

    PubMed  CAS  Google Scholar 

  11. Omeis IA, Hsu YC, Perin MS. Mouse and human neuronal pentraxin 1 (NPTX1): conservation, genomic structure, and chromosomal localization. Genomics 1996;36:543–5.

    Article  PubMed  CAS  Google Scholar 

  12. Schlimgen AK, Helms JA, Vogel H, Perin MS. Neuronal pentraxin, a secreted protein with homology to acute phase proteins of the immune system. Neuron 1995;14:519–26.

    Article  PubMed  CAS  Google Scholar 

  13. Hsu YC, Perin MS. Human neuronal pentraxin II (NPTX2): conservation, genomic structure, and chromosomal localization. Genomics 1995;28:220–27.

    Article  PubMed  CAS  Google Scholar 

  14. Tsui CC, Copeland NG, Gilbert DJ, Jenkins NA, Barnes C, Worley PF. Narp, a novel member of the pentraxin family, promotes neurite outgrowth and is dynamically regulated by neuronal activity. J Neurosci 1996;16:2463–78.

    PubMed  CAS  Google Scholar 

  15. Dodds DC, Omeis IA, Cushman SJ, Helms JA, Perin MS. Neuronal pentraxin receptor, a novel putative integral membrane pentraxin that interacts with neuronal pentraxin 1 and 2 and taipoxin-associated calcium-binding protein 49. J Biol Chem 1997;272:21488–94.

    Article  PubMed  CAS  Google Scholar 

  16. Kirkpatrick LL, Matzuk MM, Dodds DC, Perin MS. Biochemical interactions of the neuronal pentraxins. Neuronal pentraxin (NP) receptor binds to taipoxin and taipoxin-associated calcium-binding protein 49 via NP1 and NP2. J Biol Chem 2000;275:17786–92.

    Article  PubMed  CAS  Google Scholar 

  17. Bottazzi B, Vouret-Craviari V, Bastone A, De Gioia L, Matteucci C, Peri G, Spreafico F, Pausa M, D’ettorre C, Gianazza E, Tagliabue A, Salmona M, Tedesco F, Introna M, Mantovani A. Multimer formation and ligand recognition by the long pentraxin PTX3. Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component. J Biol Chem 1997;272:32817–23.

    Article  PubMed  CAS  Google Scholar 

  18. Nauta AJ, Bottazzi B, Mantovani A, Salvatori G, Kishore U, Schwaeble WJ, Gingras AR, Tzima S, Vivanco F, Egido J, Tijsma O, Hack EC, Daha MR, Roos A. Biochemical and functional characterization of the interaction between pentraxin 3 and C1q. Eur. J. Immunol 2003;33:465–73.

    Article  PubMed  CAS  Google Scholar 

  19. Roumenina LT, Ruseva MM, Zlatarova A, Ghai R, Kolev M, Olova N, Gadjeva M, Agrawal A, Bottazzi B, Mantovani A, Reid KB, Kishore U, Kojouharova MS. Interaction of C1q with IgG1, C-reactive protein and pentraxin 3: mutational studies using recombinant globular head modules of human C1q A, B, and C chains. Biochemistry 2006;45:4093–104.

    Article  PubMed  CAS  Google Scholar 

  20. Hicks PS, Saunero-Nava L, Du Clos TW, Mold C. Serum amyloid P component binds to histones and activates the classical complement pathway. J Immunol 1992;149:3689–94.

    PubMed  CAS  Google Scholar 

  21. Inforzato A, Peri G, Doni A, Garlanda C, Mantovani A, Bastone A, Carpentieri A, Amoresano A, Pucci P, Roos A, Daha MR, Vincenti S, Gallo G, Carminati P, De Santis R, Salvatori G. Structure and function of the long pentraxin PTX3 glycosidic moiety: fine-tuning of the interaction with C1q and complement activation. Biochemistry 2006;45:11540–51.

    Article  PubMed  CAS  Google Scholar 

  22. Jarva H, Jokiranta TS, Hellwage J, Zipfel PF, Meri S. Regulation of complement activation by C-reactive protein: targeting the complement inhibitory activity of factor H by an interaction with short consensus repeat domains 7 and 8–11. J Immunol 1999;163:3957–62.

    PubMed  CAS  Google Scholar 

  23. Rovere P, Peri G, Fazzini F, Bottazzi B, Doni A, Bondanza A, Zimmermann VS, Garlanda C, Fascio U, Sabbadini MG, Rugarli C, Mantovani A, Manfredi AA. The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells. Blood 2000;96:4300–6.

    PubMed  CAS  Google Scholar 

  24. Pepys MB, Booth SE, Tennent GA, Butler PJ, 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;97:152–7.

    Article  PubMed  CAS  Google Scholar 

  25. Rusnati M, Camozzi M, Moroni E, Bottazzi B, Peri G, Indraccolo S, Amadori A, Mantovani A, Presta M. Selective recognition of fibroblast growth factor-2 by the long pentraxin PTX3 inhibits angiogenesis. Blood 2004;104:92–9.

    Article  PubMed  CAS  Google Scholar 

  26. Camozzi M, Rusnati M, Bugatti A, Bottazzi B, Mantovani A, Bastone A, Inforzato A, Vincenti S, Bracci L, Mastroianni D, Presta M. Identification of an antiangiogenic FGF2-binding site in the N terminus of the soluble pattern recognition receptor PTX3. J Biol Chem 2006;281:22605–13.

    Article  PubMed  CAS  Google Scholar 

  27. Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A, Bottazzi B, Doni A, Bastone A, Mantovani G, Beck Peccoz P, Salvatori G, Mahoney DJ, Day AJ, Siracusa G, Romani L, Mantovani A. PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development 2004;131:1577–86.

    Article  PubMed  CAS  Google Scholar 

  28. Milner CM, Day AJ. TSG-6: a multifunctional protein associated with inflammation. J Cell Sci 2003;116:1863–73.

    Article  PubMed  CAS  Google Scholar 

  29. Milner CM, Higman VA, Day AJ. TSG-6: a pluripotent inflammatory mediator? Biochem Soc Trans 2006;34:446–50.

    Article  PubMed  CAS  Google Scholar 

  30. Jeannin P, Bottazzi B, Sironi M, Doni A, Rusnati M, Presta M, Maina V, Magistrelli G, Haeuw JF, Hoeffel G, Thieblemont N, Corvaia N, Garlanda C, Delneste Y, Mantovani A. Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity 2005;22:551–60.

    Article  PubMed  CAS  Google Scholar 

  31. Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, Maccagno A, Riva F, Bottazzi B, Peri G, Doni A, Vago L, Botto M, De Santis R, Carminati P, Siracusa G, Altruda F, Vecchi A, Romani L, Mantovani A. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 2002;420:182–6.

    Article  PubMed  CAS  Google Scholar 

  32. Diniz SN, Nomizo R, Cisalpino PS, Teixeira MM, Brown GD, Mantovani A, Gordon S, Reis LF, Dias AA. PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages. J Leukoc Biol 2004;75:649–56.

    Article  PubMed  CAS  Google Scholar 

  33. Bozza S, Bistoni F, Gaziano R, Pitzurra L, Zelante T, Bonifazi P, Perruccio K, Bellocchio S, Neri M, Iorio AM, Salvatori G, De Santis R, Calvitti M, Doni A, Garlanda C, Mantovani A, Romani L. Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation. Blood 2006;108:3387–96.

    Article  PubMed  CAS  Google Scholar 

  34. Szalai AJ, Agrawal A, Greenhough TJ, Volanakis JE. C-reactive protein: structural biology and host defense function. Clin Chem Lab Med 1999;37:265–70.

    Article  PubMed  CAS  Google Scholar 

  35. Breviario F, D’aniello EM, Golay J, Peri G, Bottazzi B, Bairoch A, Saccone S, Marzella R, Predazzi V, Rocchi M, et al. Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. J Biol Chem 1992;267:22190–7.

    PubMed  CAS  Google Scholar 

  36. Doni A, Peri G, Chieppa M, Allavena P, Pasqualini F, Vago L, Romani L, Garlanda C, Mantovani A. Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendritic cells. Eur J Immunol 2003;33:2886–93.

    Article  PubMed  CAS  Google Scholar 

  37. Lee GW, Lee TH, Vilcek J. TSG-14, a tumor necrosis factor- and IL-1-inducible protein, is a novel member of the pentaxin family of acute phase proteins. J Immunol 1993;150:1804–12.

    PubMed  CAS  Google Scholar 

  38. Introna M, Alles VV, Castellano M, Picardi G, De Gioia L, Bottazzai B, Peri G, Breviario F, Salmona M, De Gregorio L, Dragani TA, Srinivasan N, Blundell TL, Hamilton TA, Mantovani A. Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites. Blood 1996;87:1862–72.

    PubMed  CAS  Google Scholar 

  39. Abderrahim-Ferkoune A, Bezy O, Chiellini C, Maffei M, Grimaldi P, Bonino F, Moustaid-Moussa N, Pasqualini F, Mantovani A, Ailhaud G, Amri EZ. Characterization of the long pentraxin PTX3 as a TNFalpha-induced secreted protein of adipose cells. J Lipid Res 2003;44:994–1000.

    Article  PubMed  CAS  Google Scholar 

  40. Goodman AR, Levy DE, Reis LF, Vilcek J. Differential regulation of TSG-14 expression in murine fibroblasts and peritoneal macrophages. J Leukoc Biol 2000;67:387–95.

    PubMed  CAS  Google Scholar 

  41. Klouche M, Peri G, Knabbe C, Eckstein HH, Schmid FX, Schmitz G, Mantovani A. Modified atherogenic lipoproteins induce expression of pentraxin-3 by human vascular smooth muscle cells. Atherosclerosis 2004;175:221–8.

    Article  PubMed  CAS  Google Scholar 

  42. Agnello D, Carvelli L, Muzio V, Villa P, Bottazzi B, Polentarutti N, Mennini T, Mantovani A, Ghezzi P. Increased peripheral benzodiazepine binding sites and pentraxin 3 expression in the spinal cord during EAE: relation to inflammatory cytokines and modulation by dexamethasone and rolipram. J Neuroimmunol 2000;109:105–11.

    Article  PubMed  CAS  Google Scholar 

  43. Nauta AJ, De Haij S, Bottazzi B, Mantovani A, Borrias MC, Aten J, Rastaldi MP, Daha MR, Van Kooten C, Roos A. Human renal epithelial cells produce the long pentraxin PTX3. Kidney Int 2005;67:543–53.

    Article  PubMed  CAS  Google Scholar 

  44. Dos Santos CC, Han B, Andrade CF, Bai X, Uhlig S, Hubmayr R, Tsang M, Lodyga M, Keshavjee S, Slutsky AS, Liu M. DNA microarray analysis of gene expression in alveolar epithelial cells in response to TNFalpha, LPS, and cyclic stretch. Physiol Genomics 2004;19:331–42.

    Article  PubMed  CAS  Google Scholar 

  45. Malaguarnera L, Pilastro MR, Vicari L, Di Marco R, Malaguarnera M, Messina A. PTX3 gene expression in Castleman’s disease. Eur J Haematol 2000;64:132–4.

    Article  PubMed  CAS  Google Scholar 

  46. Klouche M, Brockmeyer N, Knabbe C, Rose-John S. Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi’s sarcoma cells. Aids 2002;16:F9–18.

    Article  PubMed  CAS  Google Scholar 

  47. Ehrt S, Schnappinger D, Bekiranov S, Drenkow J, Shi S, Gingeras TR, Gaasterland T, Schoolnik G, Nathan C. Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase. J Exp Med 2001;194:1123–40.

    Article  PubMed  CAS  Google Scholar 

  48. Goodman AR, Cardozo T, Abagyan R, Altmeyer A, Wisniewski HG, Vilcek J. Long pentraxins: an emerging group of proteins with diverse functions. Cytokine Growth Factor Rev 1996;7:191–202.

    Article  PubMed  CAS  Google Scholar 

  49. Polentarutti N, Picardi G, Basile A, Cenzuales S, Rivolta A, Matteucci C, Peri G, Mantovani A, Introna M. Interferon-gamma inhibits expression of the long pentraxin PTX3 in human monocytes. Eur J Immunol 1998;28:496–501.

    Article  PubMed  CAS  Google Scholar 

  50. Perrier P, Martinez FO, Locati M, Bianchi G, Nebuloni M, Vago G, Bazzoni F, Sozzani S, Allavena P, Mantovani A. Distinct transcriptional programs activated by interleukin-10 with or without lipopolysaccharide in dendritic cells: induction of the B cell-activating chemokine, CXC chemokine ligand 13. J Immunol 2004;172:7031–42.

    PubMed  CAS  Google Scholar 

  51. Lang R, Patel D, Morris JJ, Rutschman RL, Murray PJ. Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol 2002;169:2253–63.

    PubMed  CAS  Google Scholar 

  52. Moore KW, De Waal Malefyt R, Coffman RL, O’garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001;19:683–765.

    Article  PubMed  CAS  Google Scholar 

  53. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004;25:677–86.

    Article  PubMed  CAS  Google Scholar 

  54. Rolph MS, Zimmer S, Bottazzi B, Garlanda C, Mantovani A, Hansson GK. Production of the long pentraxin PTX3 in advanced atherosclerotic plaques. Arterioscler. Thromb Vasc Biol 2002;22:e10–4.

    Article  Google Scholar 

  55. Bosutti A, Grassi G, Zanetti M, Aleksova A, Zecchin M, Sinagra G, Biolo G, Guarnieri G. Relation between the plasma levels of LDL-cholesterol and the expression of the early marker of inflammation long pentraxin PTX3 and the stress response gene p66ShcA in pacemaker-implanted patients. Clin Exp Med 2007;7:16–23.

    Article  PubMed  CAS  Google Scholar 

  56. Varani S, Elvin JA, Yan C, Demayo J, Demayo FJ, Horton HF, Byrne MC, Matzuk MM. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol 2002;16:1154–67.

    Article  PubMed  CAS  Google Scholar 

  57. Willeke F, Assad A, Findeisen P, Schromm E, Grobholz R, Von Gerstenbergk B, Mantovani A, Peri S, Friess HH, Post S, Von Knebel Doeberitz M, Schwarzbach MH. Overexpression of a member of the pentraxin family (PTX3) in human soft tissue liposarcoma. Eur J Cancer 2006;42:2639–46.

    Article  PubMed  CAS  Google Scholar 

  58. Jaillon S, Peri G, Delneste Y, Fremaux I, Doni A, Moalli F, Garlanda C, Romani L, Gascan H, Bellocchio S, Bozza S, Cassatella MA, Jeannin P, Mantovani A. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps. J Exp Med 2007;204:793–804.

    Article  PubMed  CAS  Google Scholar 

  59. Peri G, Introna M, Corradi D, Iacuitti G, Signorini S, Avanzini F, Pizzetti F, Maggioni AP, Moccetti T, Metra M, Cas LD, Ghezzi P, Sipe JD, Re G, Olivetti G, Mantovani A, Latini R. PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans. Circulation 2000;102:636–41.

    PubMed  CAS  Google Scholar 

  60. Latini R, Maggioni AP, Peri G, Gonzini L, Lucci D, Mocarelli P, Vago L, Pasqualini F, Signorini S, Soldateschi D, Tarli L, Schweiger C, Fresco C, Cecere R, Tognoni G, Mantovani A. Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction. Circulation 2004;110:2349–54.

    Article  PubMed  CAS  Google Scholar 

  61. Cenci E, Perito S, Enssle K, Mosci P, Latge J, Romani L, Bistoni F. Th1 and Th2 cytokines in mice with invasive aspergillosis. Infect Immun 1997;65:564–70.

    PubMed  CAS  Google Scholar 

  62. Nagai H, Guo J, Choi H, Kurup V. Interferon-gamma and tumor necrosis factor-alpha protect mice from invasive aspergillosis. J Infect Dis 1995;172:1554–60.

    PubMed  CAS  Google Scholar 

  63. Gaziano R, Bozza S, Bellocchio S, Perruccio K, Montagnoli C, Pitzurra L, Salvatori G, De Santis R, Carminati P, Mantovani A, Romani L. Anti-Aspergillus fumigatus efficacy of pentraxin 3 alone and in combination with antifungals. Antimicrob Agents Chemother 2004;48:4414–21.

    Article  PubMed  CAS  Google Scholar 

  64. Soares AC, Souza DG, Pinho V, Vieira AT, Nicoli JR, Cunha FQ, Mantovani A, Reis LF, Dias AA, Teixeira MM. Dual function of the long pentraxin PTX3 in resistance against pulmonary infection with Klebsiella pneumoniae in transgenic mice. Microbes Infect 2006;8:1321–9.

    Article  PubMed  CAS  Google Scholar 

  65. Dias AA, Goodman AR, Dos Santos JL, Gomes RN, Altmeyer A, Bozza PT, Horta MF, Vilcek J, Reis LF. TSG-14 transgenic mice have improved survival to endotoxemia and to CLP-induced sepsis. J Leukoc Biol 2001;69:928–36.

    PubMed  CAS  Google Scholar 

  66. Souza DG, Soares AC, Pinho V, Torloni H, Reis LF, Teixeira MM, Dias AA. Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14 transgenic mice after ischemia and reperfusion injury. Am J Pathol 2002;160:1755–65.

    PubMed  CAS  Google Scholar 

  67. Ravizza T, Moneta D, Bottazzi B, Peri G, Garlanda C, Hirsch E, Richards GJ, Mantovani A, Vezzani A. Dynamic induction of the long pentraxin PTX3 in the CNS after limbic seizures: evidence for a protective role in seizure-induced neurodegeneration. Neuroscience 2001;105:43–53.

    Article  PubMed  CAS  Google Scholar 

  68. Van Rossum AP, Fazzini F, Limburg PC, Manfredi AA, Rovere-Querini P, Mantovani A, Kallenberg CG. The prototypic tissue pentraxin PTX3, in contrast to the short pentraxin serum amyloid P, inhibits phagocytosis of late apoptotic neutrophils by macrophages. Arthritis Rheum 2004;50:2667–74.

    Article  PubMed  CAS  Google Scholar 

  69. Baruah P, Propato A, Dumitriu IE, Rovere-Querini P, Russo V, Fontana R, Accapezzato D, Peri G, Mantovani A, Barnaba V, Manfredi AA. The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens. Blood 2006;107:151–8.

    Article  PubMed  CAS  Google Scholar 

  70. Castellano G, Woltman AM, Nauta AJ, Roos A, Trouw LA, Seelen MA, Schena FP, Daha MR, Van Kooten C. Maturation of dendritic cells abrogates C1q production in vivo and in vitro. Blood 2004;103:3813–20.

    Article  PubMed  CAS  Google Scholar 

  71. Baruah P, Dumitriu IE, Peri G, Russo V, Mantovani A, Manfredi AA, Rovere-Querini P. The tissue pentraxin PTX3 limits C1q-mediated complement activation and phagocytosis of apoptotic cells by dendritic cells. J Leukoc Biol 2006.

  72. Nauta AJ, Daha MR, Van Kooten C, Roos A. Recognition and clearance of apoptotic cells: a role for complement and pentraxins. Trends Immunol 2003;24:148–54.

    Article  PubMed  CAS  Google Scholar 

  73. Jeannin P, Renno T, Goetsch L, Miconnet I, Aubry JP, Delneste Y, Herbault N, Baussant T, Magistrelli G, Soulas C, Romero P, Cerottini JC, Bonnefoy JY. OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway. Nat Immunol 2000;1:502–9.

    Article  PubMed  CAS  Google Scholar 

  74. Baruah P, Trimarchi M, Dumitriu IE, Dellantonio G, Doglioni C, Rovere-Querini P, Bussi M, Manfredi AA. Innate responses to Aspergillus: role of C1q and pentraxin 3 in nasal polyposis. Am J Rhinol 2007;21:224–30.

    Article  PubMed  Google Scholar 

  75. Camozzi M, Zacchigna S, Rusnati M, Coltrini D, Ramirez-Correa G, Bottazzi B, Mantovani A, Giacca M, Presta M. Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo. Arterioscler Thromb Vasc Biol 2005;25:1837–42.

    Article  PubMed  CAS  Google Scholar 

  76. Zhang X, Jafari N, Barnes RB, Confino E, Milad M, Kazer RR. Studies of gene expression in human cumulus cells indicate pentraxin 3 as a possible marker for oocyte quality. Fertil Steril 2005;83(Suppl 1):1169–79.

    Article  PubMed  CAS  Google Scholar 

  77. Tranguch S, Chakrabarty A, Guo Y, Wang H, Dey SK. Maternal Pentraxin 3 Deficiency Compromises Implantation in Mice. Biol Reprod 2007.

  78. Hess AP, Hamilton AE, Talbi S, Dosiou C, Nyegaard M, Nayak N, Genbecev-Krtolica O, Mavrogianis P, Ferrer K, Kruessel J, Fazleabas AT, Fisher SJ, Giudice LC. Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biol Reprod 2007;76:102–17.

    Article  PubMed  CAS  Google Scholar 

  79. Muller B, Peri G, Doni A, Torri V, Landmann R, Bottazzi B, Mantovani A. Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients. Crit Care Med 2001;29:1404–7.

    Article  PubMed  CAS  Google Scholar 

  80. Napoleone E, Di Santo A, Peri G, Mantovani A, De Gaetano G, Donati MB, Lorenzet R. The long pentraxin PTX3 up-regulates tissue factor in activated monocytes: another link between inflammation and clotting activation. J Leukoc Biol 2004;76:203–9.

    Article  PubMed  CAS  Google Scholar 

  81. Napoleone E, Di Santo A, Bastone A, Peri G, Mantovani A, De Gaetano G, Donati MB, Lorenzet R. Long pentraxin PTX3 upregulates tissue factor expression in human endothelial cells: a novel link between vascular inflammation and clotting activation. Arterioscler Thromb Vasc Biol 2002;22:782–7.

    Article  PubMed  CAS  Google Scholar 

  82. Mairuhu AT, Peri G, Setiati TE, Hack CE, Koraka P, Soemantri A, Osterhaus AD, Brandjes DP, Van Der Meer JW, Mantovani A, Van Gorp EC. Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections. J Med Virol 2005;76:547–52.

    Article  PubMed  CAS  Google Scholar 

  83. Azzurri A, Sow OY, Amedei A, Bah B, Diallo S, Peri G, Benagiano M, D’elios MM, Mantovani A, Del Prete G. IFN-gamma-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection. Microbes Infect 2005;7:1–8.

    Article  PubMed  CAS  Google Scholar 

  84. Olesen R, Wejse C, Velez DR, Bisseye C, Sodemann M, Aaby P, Rabna P, Worwui A, Chapman H, Diatta M, Adegbola RA, Hill PC, Ostergaard L, Williams SM, Sirugo G. DC-SIGN (CD209), Pentraxin 3 and Vitamin D Receptor gene variants associate with pulmonary tubercolosis risk in West-Africans. Genes and Immunity, 2007 (in press).

  85. Inoue K, Sugiyama A, Reid PC, Ito Y, Miyauchi K, Mukai S, Sagara M, Miyamoto K, Satoh H, Kohno I, Kurata T, Ota H, Mantovani A, Hamakubo T, Daida H, Kodama T. Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris. Arterioscler Thromb Vasc Biol 2007;27:161–7.

    Article  PubMed  CAS  Google Scholar 

  86. Kotooka N, Inoue T, Fujimatsu D, Morooka T, Hashimoto S, Hikichi Y, Uchida T, Sugiyama A, Node K. Pentraxin3 is a novel marker for stent-induced inflammation and neointimal thickening. Atherosclerosis, 2007.

  87. Fazzini F, Peri G, Doni A, Dell’antonio G, Dal Cin E, Bozzolo E, D’auria F, Praderio L, Ciboddo G, Sabbadini MG, Manfredi AA, Mantovani A, Querini PR. PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum 2001;44:2841–50.

    Article  PubMed  CAS  Google Scholar 

  88. Luchetti MM, Piccinini G, Mantovani A, Peri G, Matteucci C, Pomponio G, Fratini M, Fraticelli P, Sambo P, Di Loreto C, Doni A, Introna M, Gabrielli A. Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA). Clin Exp Immunol 2000;119:196–202.

    Article  PubMed  CAS  Google Scholar 

  89. Van Rossum AP, Pas HH, Fazzini F, Huitema MG, Limburg PC, Jonkman MF, Kallenberg CG. Abundance of the long pentraxin PTX3 at sites of leukocytoclastic lesions in patients with small-vessel vasculitis. Arthritis Rheum 2006;54:986–91.

    Article  PubMed  CAS  Google Scholar 

  90. Tong M, Carrero JJ, Qureshi AR, Anderstam B, Heimburger O, Barany P, Axelsson J, Alverstrand A, Stenvinkel P, Lindholm B, Suliman M. Plasma Pentraxin 3 in chronic kidney disease patients: association with renal function, protein-energy wasting, cardiovascular disease and mortality. Clin J Am Soc Nephrol, 2007;2:889–97.

    Article  PubMed  CAS  Google Scholar 

  91. Boehme M, Kaehne F, Kuehne A, Bernhardt W, Schroder M, Pommer W, Fischer C, Becker H, Muller C, Schindler R. Pentraxin 3 is elevated in haemodialysis patients and is associated with cardiovascular disease. Nephrol Dial Transplant, 2007.

  92. Paffoni A, Ragni G, Doni A, Somigliana E, Pasqualini F, Restelli L, Pardi G, Mantovani A, Garlanda C. Follicular fluid levels of the long pentraxin PTX3. J Soc Gynecol Investig 2006;13:226–31.

    Article  PubMed  CAS  Google Scholar 

  93. Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999;180:499–506.

    Article  PubMed  CAS  Google Scholar 

  94. Cetin I, Cozzi V, Pasqualini F, Nebuloni M, Garlanda C, Vago L, Pardi G, Mantovani A. Elevated maternal levels of the long pentraxin 3 (PTX3) in preeclampsia and intrauterine growth restriction. Am J Obstet Gynecol 2006;194:1347–53.

    Article  PubMed  CAS  Google Scholar 

  95. Rovere-Querini P, Antonacci S, Dell’antonio G, Angeli A, Almirante G, Cin ED, Valsecchi L, Lanzani C, Sabbadini MG, Doglioni C, Manfredi AA, Castiglioni MT. Plasma and tissue expression of the long pentraxin 3 during normal pregnancy and preeclampsia. Obstet Gynecol 2006;108:148–55.

    PubMed  Google Scholar 

  96. Benyo DF, Smarason A, Redman CW, Sims C, Conrad KP. Expression of inflammatory cytokines in placentas from women with preeclampsia. J Clin Endocrinol Metab 2001;86:2505–12.

    Article  PubMed  CAS  Google Scholar 

  97. Rinehart BK, Terrone DA, Lagoo-Deenadayalan S, Barber WH, Hale EA, Martin JN, Jr., Bennett WA. Expression of the placental cytokines tumor necrosis factor alpha, interleukin 1beta, and interleukin 10 is increased in preeclampsia. Am J Obstet Gynecol 1999;181:915–20.

    Article  PubMed  CAS  Google Scholar 

  98. Assi F, Fruscio R, Bonardi C, Ghidini A, Allavena P, Mantovani A, Locatelli A. Pentraxin 3 in plasma and vaginal fluid in women with preterm delivery. Bjog 2007;114:143–7.

    PubMed  CAS  Google Scholar 

  99. Hirschfield GM, Gallimore JR, Kahan MC, Hutchinson WL, Sabin CA, Benson GM, Dhillon AP, Tennent GA, Pepys MB. Transgenic human C-reactive protein is not proatherogenic in apolipoprotein E-deficient mice. Proc Natl Acad Sci USA 2005;102:8309–14.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

The contribution of the European Commission (MUGEN, MUVAPRED), Ministero dell’Istruzione, Università e Ricerca (MIUR; project FIRB), Telethon (Telethon grant n. GGP05095), fondazione CARIPLO (project Nobel) and the Italian Association for Cancer Research (AIRC) is gratefully acknowledged.

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  1. Istituto Clinico Humanitas, via Manzoni 56, 20089, Milan, Rozzano, Italy

    Alberto Mantovani, Cecilia Garlanda, Andrea Doni & Barbara Bottazzi

  2. Institute of General Pathology, Faculty of Medicine, University of Milan, Milan, 20100, Italy

    Alberto Mantovani

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  1. Alberto Mantovani
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  2. Cecilia Garlanda
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  3. Andrea Doni
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  4. Barbara Bottazzi
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Correspondence to Alberto Mantovani.

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Mantovani, A., Garlanda, C., Doni, A. et al. Pentraxins in Innate Immunity: From C-Reactive Protein to the Long Pentraxin PTX3. J Clin Immunol 28, 1–13 (2008). https://doi.org/10.1007/s10875-007-9126-7

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  • DOI: https://doi.org/10.1007/s10875-007-9126-7

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