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  • 1 Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt 62, H-6726, Szeged, Hungary
  • | 2 Biotechnology, Gedeon Richter Ltd., Gyömrői út 19-21, H-1103, Budapest, Hungary
  • | 3 Medical Gene Technology Unit, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083, Budapest, Hungary
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Abstract

Serum amyloid P component (SAP), a member of the innate immune system, does not penetrate the brain in physiological conditions; however, SAP is a stabilizing component of the amyloid plaques in neurodegenerative diseases. We investigated the cerebrovascular transport of human SAP in animal experiments and in culture blood-brain barrier (BBB) models. After intravenous injection, no SAP could be detected by immunohistochemistry or ELISA in healthy rat brains. Salmonella typhimurium lipopolysaccharide injection increased BBB permeability for SAP and the number of cerebral vessels labeled with fluorescein isothiocyanate (FITC)-SAP in mice. Furthermore, when SAP was injected to the rat hippocampus, a time-dependent decrease in brain concentration was seen demonstrating a rapid SAP efflux transport in vivo. A temperature-dependent bidirectional transport of FITC-SAP was observed in rat brain endothelial monolayers. The permeability coefficient for FITC-SAP was significantly higher in abluminal to luminal (brain to blood) than in the opposite direction. The luminal release of FITC-SAP from loaded endothelial cells was also significantly higher than the abluminal one. Our data indicate the presence of BBB efflux transport mechanisms protecting the brain from SAP penetration. Damaged BBB integrity due to pathological insults may increase brain SAP concentration contributing to development of neurodegenerative diseases.

  • 1. M Skinner AS Cohen 1988 Amyloid P component Methods Enzymol 163 523 536.

  • 2. CJ de Haas 1999 New insights into the role of serum amyloid P component, a novel lipopolysaccharide-binding protein FEMS Immunol Med Microbiol 26 197 202.

    • Search Google Scholar
    • Export Citation
  • 3. M Noursadeghi MCM Bickerstaff JR Gallimore J Herbert J Cohen 2000 Role of serum amyloid P component in bacterial infection: protection of the host or protection of the pathogen Proc Natl Acad Sci USA 97 14584 14589.

    • Search Google Scholar
    • Export Citation
  • 4. MB Pepys JR Gallimore J Lloyd Z Li D Graham GW Taylor 2012 Isolation and characterization of pharmaceutical grade human pentraxins, serum amyloid P component and C-reactive protein, for clinical use J Immunol Meth 384 92 102.

    • Search Google Scholar
    • Export Citation
  • 5. GD Armstrong GL Mulvey P Marcato TP Griener MC Kahan 2006 Human serum amyloid P component protects against Escherichia coli O157:H7 Shiga toxin 2 in vivo: therapeutic implications for hemolytic-uremic syndrome J Infect Dis 193 1120 1124.

    • Search Google Scholar
    • Export Citation
  • 6. J Yuste M Botto SE Bottoms JS Brown 2007 Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae PLoS Pathog 3 e120.

    • Search Google Scholar
    • Export Citation
  • 7. ER Job B Bottazzi B Gilbertson KM Edenborough LE Brown 2013 Serum amyloid P is a sialylated glycoprotein inhibitor of influenza A viruses PLoS ONE 8 e59623.

    • Search Google Scholar
    • Export Citation
  • 8. P Balmer F McMonagle J Alexander RS Philips 2000 Experimental erythrocytic malaria infection induces elevated serum amyloid P production in mice Immunol Lett 72 147 152.

    • Search Google Scholar
    • Export Citation
  • 9. KB Gilchrist MC Garcia R Sobonya PN Lipke SA Klotz 2012 New features of invasive Candidiasis in humans, Amyloid formation by fungi and deposition of serum amyloid P component by the host J Infect Dis 206 1473 1478.

    • Search Google Scholar
    • Export Citation
  • 10. AS Maharjan D Roife D Brazill RH Goner 2013 Serum amyloid P inhibits granulocyte adhesion Fibrog Tissue Repair 6 2.

  • 11. MB Pepys 2001 Pathogenesis, diagnosis and treatment of systemic amyloidosis Philos Trans R Soc Lond B Biol Sci 356 203 210.

  • 12. K Bodin S Ellmerich MC Kahan GA Tennent A Loesch 2010 Antibodies to human serum amyloid P component eliminate visceral amyloid deposits Nature 468 93 97.

    • Search Google Scholar
    • Export Citation
  • 13. MB Pepys J Herbert WL Hutchinson GA Tennent HJ Lachmann 2002 Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis Nature 417 254 259.

    • Search Google Scholar
    • Export Citation
  • 14. JD Gillmore GA Tennent WL Hutchinson JR Gallimore HJ Lachmann 2010 Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis Br J Haematol 148 760 767.

    • Search Google Scholar
    • Export Citation
  • 15. SE Kolstoe BH Ridha V Bellotti N Wang CV Robinson 2009 Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid component Proc Natl Acad Sci USA 106 7619 7623.

    • Search Google Scholar
    • Export Citation
  • 16. S Inoue M Kuroiwa R Kisilevsky 1999 Basement membranes, microfibrils and beta amyloid fibrillogenesis in Alzheimer's disease: high resolution ultrastructural findings Brain Res Rev 29 218 231.

    • Search Google Scholar
    • Export Citation
  • 17. EG McGeer K Yasojima C Schwab PL McGeer 2001 The pentraxins: possible role in Alzheimer's disease and other innate inflammatory diseases Neurobiol Aging 22 843 848.

    • Search Google Scholar
    • Export Citation
  • 18. J Ghiso B Frangione 2002 Amyloidosis and Alzheimer's disease Adv Drug Deliv Rev 54 1539 1551.

  • 19. F Coria E Castaño F Prelli M Larondo-Lillo S van Duinen 1988 Isolation and characterization of amyloid P component from Alzheimer's disease and other types of cerebral amyloidosis Lab Invest 58 454 458.

    • Search Google Scholar
    • Export Citation
  • 20. RN Kalaria I Grahovac 1990 Serum amyloid P immunoreactivity in hippocampal tangles, plaques and vessels: implications for leakage across the blood-brain barrier in Alzheimer's disease Brain Res 516 349 353.

    • Search Google Scholar
    • Export Citation
  • 21. RN Kalaria TE Golde ML Cohen SG Younkin 1991 Serum amyloid P in Alzheimer's disease. Implications for dysfunction of the blood-brain barrier Ann N Y Acad Sci 640 145 148.

    • Search Google Scholar
    • Export Citation
  • 22. LS Perlmutter E Barrón M Myers D Saperia HC Chui 1995 Localization of amyloid P component in human brain: vascular staining patterns and association with Alzheimer's disease lesions J Comp Neurol 352 92 105.

    • Search Google Scholar
    • Export Citation
  • 23. A Rostagno T Lashley D Ng J Meyerson H Braendgaard 2007 Preferential association of serum amyloid P component with fibrillar deposits in familial British and Danish dementias: similarities with Alzheimer's disease J Neurol Sci 257 88 96.

    • Search Google Scholar
    • Export Citation
  • 24. K Yasojima C Schwab EG McGeer PL McGeer 2000 Human neurons generate C-reactive protein and amyloid P: upregulation in Alzheimer's disease Brain Res 887 80 89.

    • Search Google Scholar
    • Export Citation
  • 25. R Veerhuis RS Boshuizen M Morbin G Mazzoleni JJM Hoozemans 2005 Activation of human microglia by fibrillar prion protein-related peptides in enhanced by amyloid-associated factors SAP and C1q Neurobiol Dis 19 273 282.

    • Search Google Scholar
    • Export Citation
  • 26. Z Urbányi V Lakics SL Erdő 1994 Serum amyloid P component- induced cell death in primary cultures of rat cerebral cortex Eur J Pharmacol 270 375 378.

    • Search Google Scholar
    • Export Citation
  • 27. Z Urbányi L László TB Tomasi E Tóth Mekes 2003 Serum amyloid P component induces neuronal apoptosis and β-amyloid immunoreactivity Brain Res 988 69 77.

    • Search Google Scholar
    • Export Citation
  • 28. Z Urbányi E Forrai M Sárvári I Likó J Illés 2005 Glycosaminoglycans inhibit neurodegenerative effects of serum amyloid P component in vitro Neurochem Int 46 471 477.

    • Search Google Scholar
    • Export Citation
  • 29. Z Urbányi M Sass J Laszy V Takács I Gyertyán 2007 Serum amyloid P component induces TUNEL-positive nuclei in rat brain after intrahippocampal administration Brain Res 1145 221 226.

    • Search Google Scholar
    • Export Citation
  • 30. MB Pepys GA Tennent DR Booth V Bellotti LB Lovat 1996 Molecular mechanisms of fibrillogenesis and the protective role of amyloid P component: two possible avenues for therapy Ciba Found Symp 199 73 89.

    • Search Google Scholar
    • Export Citation
  • 31. PL Jager BP Hazenberg EJ Franssen PC Limburg MH van Rijswijk 1998 Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value J Nucl Med 29 699 706.

    • Search Google Scholar
    • Export Citation
  • 32. JR Crawford NL Bjorklund G Taglialatela RH Gomer 2012 Brain serum amyloid P levels are reduced in individuals that lack dementia while having Alzheimer's disease neuropathology Neurochem Res 37 795 801.

    • Search Google Scholar
    • Export Citation
  • 33. PN Hawkins MN Rossor JP Gallimore B Miller EG Moore 1994 Concentration of serum amyloid P component in CSF as a possible marker of cerebral amyloid deposits in Alzheimer's disease Biochem Biophys Res Commun 201 722 726.

    • Search Google Scholar
    • Export Citation
  • 34. M Kimura T Asada M Uno N Machida K Kasuya 1999 Assessment of cerebrospinal fluid levels of serum amyloid P component in patients with Alzheimer's disease Neurosci Lett 273 137 139.

    • Search Google Scholar
    • Export Citation
  • 35. C Mulder SNM Schoonenboom L-O Wahlund P Scheltens GJ van Kamp 2002 CSF markers related to pathogenetic mechanisms in Alzheimer's disease J Neural Transm 109 1491 1498.

    • Search Google Scholar
    • Export Citation
  • 36. NA Verwey A Schuitemaker WM van der Flier SD Mulder C Mulder 2008 Serum amyloid P component as a biomarker in mild cognitive impairment and Alzheimer's disease Dement Geriatr Cogn Disord 26 522 527.

    • Search Google Scholar
    • Export Citation
  • 37. SD Mulder CE Hack WM van der Flier P Scheltens MA Blankenstein 2010 Evaluation of intrathecal serum amyloid P (SAP) and C-reactive protein (CRP) synthesis in Alzheimer's disease with the use of index values J Alzheimer's Dis 22 1073 1079.

    • Search Google Scholar
    • Export Citation
  • 38. S Veszelka Kittel MA Deli 2011 Tools of modelling blood-brain barrier K Tihanyi M Vastag Solubility, Delivery, and ADME Problems of Drugs and Drug-Candidates Bentham Science Publishers Washington 166 188.

    • Search Google Scholar
    • Export Citation
  • 39. H Xaio WA Banks ML Niehoff JE Morley 2001 Effect of LPS on the permeability of the blood-brain barrier to insulin Brain Res 896 36 42.

    • Search Google Scholar
    • Export Citation
  • 40. S Veszelka Z Urbányi T Pázmány L Németh I Obál 2003 Human serum amyloid P component attenuates the bacterial lipopolysaccharide-induced increase in blood-brain barrier permeability in mice Neurosci Lett 352 57 60.

    • Search Google Scholar
    • Export Citation
  • 41. G Paxinos C Watson 1986 The Rat Brain in Stereotaxic Coordinates Academic Press San Diego.

  • 42. S Veszelka M Pásztói AE Farkas I Krizbai NTK Dung 2007 Pentosan polysulfate protects brain endothelial cells against bacterial lipopolysaccharide-induced damages Neurochem Int 50 219 228.

    • Search Google Scholar
    • Export Citation
  • 43. MA Deli S Veszelka B Csiszár A Tóth Kittel 2010 Protection of the blood-brain barrier by pentosan against amyloid β-induced toxicity J Alzheimer's Dis 22 777 794.

    • Search Google Scholar
    • Export Citation
  • 44. S Veszelka AE Tóth FR Walter Z Datki E Mózes 2013 Docosahexaenoic acid regulates amyloid-β induced toxicity in cells of the neurovascular unit J Alzheimer's Dis 36 487 501.

    • Search Google Scholar
    • Export Citation
  • 45. P Grammas M Yamada B Zlokovic 2002 The cerebromicrovasculature: a key player in the pathogenesis if Alzheimer's disease J Alzheimer's Dis 4 217 223.

    • Search Google Scholar
    • Export Citation
  • 46. MA Deli 2005 The role of blood-brain barrier in neurodegenerative diseases I Di Liegro G Savettieri Molecular Bases of Neurodegeneration Research Signpost Kerala 137 161.

    • Search Google Scholar
    • Export Citation
  • 47. H Wada 1998 Blood-brain barrier permeability of the demented elderly as studied by cerebrospinal fluid-serum albumin ration Intern Med 37 509 513.

    • Search Google Scholar
    • Export Citation
  • 48. A Carrano 2013 Breaking Barriers. Blood-brain barrier alterations in capillary cerebral amyloid angiopathy and Alzheimer's disease Offpage Amsterdam.

    • Search Google Scholar
    • Export Citation
  • 49. A Carrano JJ Hoozemans SM van der Vies AJ Rozemuller J van Horssen 2011 Amyloid beta induces oxidative stress-mediated blood-brain barrier changes in capillary amyloid angiopathy Antioxid Redox Signalling 15 1167 1178.

    • Search Google Scholar
    • Export Citation
  • 50. PN Hawkins MB Pepys 1995 Imaging amyloidosis with radiolabelled SAP Eur J Nucl Med 22 595 599.

  • 51. LB Lovat AAJ O'Brien SF Armstrong S Madhoo CJ Bulpitt 1998 Scintigraphy with 123I-serum amyloid P component in Alzheimer disease Alzheimer Dis Assoc Disord 12 208 210.

    • Search Google Scholar
    • Export Citation
  • 52. MR Dillingh B van der Blink M Moerland MGJ van Dongen M Levi 2013 Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis Pulm Pharmacol Ther.

    • Search Google Scholar
    • Export Citation
  • 53. AP Castaño S-L Lin T Surowy BT Nowlin SA Turlapati 2009 Serum amyloid P inhibits fibrosis through FcγR-dependent monocyte-macrophage regulation in vivo Sci Transl Med 1 5ra13.

    • Search Google Scholar
    • Export Citation
  • 54. Z Song L Cai L Guo Y Tsukamoto C Yutani 2010 Accumulation and expression of serum amyloid P component in human atherosclerotic lesions Atherosclerosis 211 90 95.

    • Search Google Scholar
    • Export Citation
  • 55. RE Tanzi RD Moir SL Wagner 2004 Clearance of Alzheimer's Aβ peptide: the many roads to perdition Neuron 43 605 608.

  • 56. BV Zlokovic 2004 Clearing amyloid through the blood-brain barrier J Neurochem 89 807 811.

  • 57. LB Jaeger S Dohgu R Sultana JL Lynch JB Owen 2009 Lipopolysaccharide alters the blood-brain barrier transport of amyloid beta protein: A mechanism for inflammation in the progression of Alzheimer's disease Brain Behav Immun 23 507 517.

    • Search Google Scholar
    • Export Citation
  • 58. MA Erickson PE Hartvigson Y Morofuji JB Owen DA Butterfield 2012 Lipopolysaccharide impairs amyloid beta efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier J Neuroinflamm 9 150.

    • Search Google Scholar
    • Export Citation
  • 59. HF Stanyon JH Viles 2012 Human serum albumin can regulate amyloid-β peptide fiber growth in the brain interstitium. Implications for Alzheimer disease J Biol Chem 287 28163 28168.

    • Search Google Scholar
    • Export Citation
  • 60. J Shi G Perry MS Berridge G Aliev SL Siedlak 2002 Labeling of cerebral amyloid β deposits in vivo using intranasal basic fibroblast growth factor and serum amyloid P component in mice J Nucl Med 43 1044 1051.

    • Search Google Scholar
    • Export Citation
  • 61. GA Tennent LB Lovat MB Pepys 1995 Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer's disease and systemic amyloidosis Proc Natl Acad Sci USA 92 4299 4903.

    • Search Google Scholar
    • Export Citation
  • 62. I Likó M Mák Klement Hunyadi-Gulyás T Pázmány 2007 Evidence for an extended interacting surface between β-amyloid and serum amyloid P component Neurosci Lett 412 51 55.

    • Search Google Scholar
    • Export Citation
  • 63. R Gupta-Bansal KR Brunden 1998 Congo red inhibits proteoglycan and serum amyloid P binding to amyloid β fibrils J Neurochem 70 292 298.

    • Search Google Scholar
    • Export Citation
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Senior editors

Editor(s)-in-Chief: Dunay, Ildiko Rita

Editor(s)-in-Chief: Heimesaat, Markus M.

Vice Editor(s)-in-Chief: Fuchs, Anja

Editorial Board

Chair of the Editorial Board:
Jeffrey S. Buguliskis (Thomas Jefferson University, USA)

  • Jörn Albring (University of Münster, Germany)
  • Stefan Bereswill (Charité - University Medicine Berlin, Germany)
  • Dunja Bruder (University of Megdeburg, Germany)
  • Jan Buer (University of Duisburg, Germany)
  • Jeff Buguliskis (Thomas Jefferson University, USA)
  • Edit Buzas (Semmelweis University, Hungary)
  • Charles Collyer (University of Sydney, Australia)
  • Renato Damatta (UENF, Brazil)
  • Ivelina Damjanova (Semmelweis University, Hungary)
  • Maria Deli (Biological Research Center, HAS, Hungary)
  • Olgica Djurković-Djaković (University of Belgrade, Serbia)
  • Jean-Dennis Docquier (University of Siena, Italy)
  • Anna Erdei (Eötvös Loránd University, Hungary)
  • Zsuzsanna Fabry (University of Washington, USA)
  • Beniam Ghebremedhin (Witten/Herdecke University, Germany)
  • Nancy Guillen (Institute Pasteur, France)
  • Georgina L. Hold (University of Aberdeen, United Kingdom)
  • Ralf Ignatius (Charité - University Medicine Berlin, Germany)
  • Zsuzsanna Izsvak (MDC-Berlin, Germany)
  • Achim Kaasch (University of Cologne, Germany)
  • Tamás Laskay (University of Lübeck, Germany)
  • Oliver Liesenfeld (Roche, USA)
  • Shreemanta Parida (Vaccine Grand Challenge Program, India)
  • Matyas Sandor (University of Wisconsin, USA)
  • Ulrich Steinhoff (University of Marburg, Germany)
  • Michal Toborek (University of Miami, USA)
  • Mary Jo Wick (University of Gothenburg, Sweden)
  • Susanne A. Wolf (MDC-Berlin, Germany)

 

Dr. Dunay, Ildiko Rita
Magdeburg, Germany
E-mail: ildikodunay@gmail.com

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European Journal of Microbiology and Immunology
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