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Table of Contents
Vol. 8, No. 5, 2011
Issue release date: June 2011
Section title: Original Paper
Free Access
Neurodegenerative Dis 2011;8:375–380
(DOI:10.1159/000324373)

Depletion of Plasma Gelsolin in Patients with Tick-Borne Encephalitis and Lyme Neuroborreliosis

Kułakowska A.a · Zajkowska J.M.b · Ciccarelli N.J.d · Mroczko B.c · Drozdowski W.a · Bucki R.d
Departments of aNeurology, bInfectious Diseases and Neuroinfections and cBiochemical Diagnostics, Medical University of Białystok, Białystok, Poland; dInstitute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pa., USA
email Corresponding Author

Abstract

Background/Aims: Cell damage during the course of inflammation results in cytoplasmic actin release, which if not eliminated by the extracellular actin scavenger system, composed of gelsolin and vitamin D binding protein, can cause dysfunction of hemostasis and toxicity towards surrounding cells. In this study, we test the hypothesis that an inflammatory reaction induced by central nervous system infections such as tick-borne encephalitis (TBE) or Lyme neuroborreliosis (LNB) will result in plasma gelsolin concentration changes in the blood and cerebrospinal fluid (CSF). Methods: Quantitative Western blot was used to determine gelsolin levels in 58 samples, which include: 29 patients without infection (diagnosed with conditions such as idiopathic cephalalgia, idiopathic Bell’s facial nerve palsy and ischialgia due to discopathy in which standard CSF diagnostic tests show no abnormalities), 12 patients diagnosed with TBE, and 17 patients diagnosed with LNB sub forma meningitis. Results and Conclusion: The gelsolin concentration in the blood of patients with TBE (163.2 ± 80.8 µg/ml) and LNB (113.6 ± 56.8 µg/ml) was significantly lower (p < 0.05 and p < 0.001, respectively) compared to the control group (226.3 ± 100.7 µg/ml). Furthermore, there was no statistically significant difference between the CSF gelsolin concentration in patients with TBE (3.9 ± 3.3 µg/ml), LNB (2.9 ± 1.2 µg/ml) and the control group (3.7 ± 3.3 µg/ml). An observed decrease in gelsolin concentration in the blood of TBE and LNB patients supports previous findings indicating the involvement of gelsolin in the pathophysiology of an inflammatory response. Therefore, evaluation of blood gelsolin concentration and administration of recombinant plasma gelsolin might provide a new tool to develop diagnostic and therapeutic strategies for TBE and LNB.

© 2011 S. Karger AG, Basel


  

Key Words

  • Plasma gelsolin
  • Cerebrospinal fluid
  • Tick-borne encephalitis
  • Lyme disease

References

  1. Osborn TM, Dahlgren C, Hartwig JH, Stossel TP: Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin. Am J Physiol Cell Physiol 2007;292:C1323–C1330.
  2. Bucki R, Kulakowska A, Byfield FJ, Zendzian-Piotrowska M, Baranowski M, Marzec M, Winer JP, Ciccarelli NJ, Gorski J, Drozdowski W, Bittman R, Janmey PA: Plasma gelsolin modulates cellular response to sphingosine-1-phosphate. Am J Physiol Cell Physiol 2010;299:C1516–C1523.
  3. Bucki R, Georges PC, Espinassous Q, Funaki M, Pastore JJ, Chaby R, Janmey PA: Inactivation of endotoxin by human plasma gelsolin. Biochemistry 2005;44:9590–9597.
  4. DiNubile MJ, Stossel TP, Ljunghusen OC, Ferrara JL, Antin JH: Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation. Blood 2002;100:4367–4371.
  5. Lee PS, Waxman AB, Cotich KL, Chung SW, Perrella MA, Stossel TP: Plasma gelsolin is a marker and therapeutic agent in animal sepsis. Crit Care Med 2007;35:849–855.
  6. Rothenbach PA, Dahl B, Schwartz JJ, O’Keefe GE, Yamamoto M, Lee WM, Horton JW, Yin HL, Turnage RH: Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction. J Appl Physiol 2004;96:25–31.
  7. Lee PS, Patel SR, Christiani DC, Bajwa E, Stossel TP, Waxman AB: Plasma gelsolin depletion and circulating actin in sepsis: a pilot study. PLoS One 2008;3:e3712.
  8. Kulakowska A, Drozdowski W, Sadzynski A, Bucki R, Janmey PA: Gelsolin concentration in cerebrospinal fluid from patients with multiple sclerosis and other neurological disorders. Eur J Neurol 2008;15:584–588.
  9. Lee PS, Sampath K, Karumanchi SA, Tamez H, Bhan I, Isakova T, Gutierrez OM, Wolf M, Chang Y, Stossel TP, Thadhani R: Plasma gelsolin and circulating actin correlate with hemodialysis mortality. J Am Soc Nephrol 2009;20:1140–1148.
  10. Hildenbrand P, Craven DE, Jones R, Nemeskal P: Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol 2009;30:1079–1087.
  11. Pachner AR, Steiner I: Lyme neuroborreliosis: infection, immunity, and inflammation. Lancet Neurol 2007;6:544–552.
  12. Fallon BA, Levin ES, Schweitzer PJ, Hardesty D: Inflammation and central nervous system Lyme disease. Neurobiol Dis 2010;37:534–541.
  13. Atrasheuskaya AV, Fredeking TM, Ignatyev GM: Changes in immune parameters and their correction in human cases of tick-borne encephalitis. Clin Exp Immunol 2003;131:148–154.
  14. Gelpi E, Preusser M, Laggner U, Garzuly F, Holzmann H, Heinz FX, Budka H: Inflammatory response in human tick-borne encephalitis: analysis of postmortem brain tissue. J Neurovirol 2006;12:322–327.
  15. Kaiser R: Tick-borne encephalitis. Infect Dis Clin North Am 2008;22:561–575, x.
  16. Mygland A, Ljostad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I: EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol 2010;17:8–16, e11–e14.
  17. Mounzer KC, Moncure M, Smith YR, DiNubile MJ: Relationship of admission plasma gelsolin levels to clinical outcomes in patients after major trauma. Am J Respir Crit Care Med 1999;160:1673–1681.
  18. Nau R, Christen HJ, Eiffert H: Lyme disease – current state of knowledge. Dtsch Arztebl Int 2009;106:72–81, quiz 82, I.
  19. Kwiatkowski DJ, Mehl R, Izumo S, Nadal-Ginard B, Yin HL: Muscle is the major source of plasma gelsolin. J Biol Chem 1988;263:8239–8243.
  20. Mansfield KL, Johnson N, Phipps LP, Stephenson JR, Fooks AR, Solomon T: Tick-borne encephalitis virus – a review of an emerging zoonosis. J Gen Virol 2009;90:1781–1794.
  21. Neuwelt EA: Mechanisms of disease: the blood-brain barrier. Neurosurgery 2004;54:131–140, discussion 141–132.
  22. Lipscomb MF, Masten BJ: Dendritic cells: immune regulators in health and disease. Physiol Rev 2002;82:97–130.
  23. Moretta A, Marcenaro E, Parolini S, Ferlazzo G, Moretta L: NK cells at the interface between innate and adaptive immunity. Cell Death Differ 2008;15:226–233.
  24. Aravalli RN, Peterson PK, Lokensgard JR: Toll-like receptors in defense and damage of the central nervous system. J Neuroimmune Pharmacol 2007;2:297–312.
  25. Bucki R, Levental I, Kulakowska A, Janmey PA: Plasma gelsolin: function, prognostic value, and potential therapeutic use. Curr Protein Pept Sci 2008;9:541–551.
  26. Smith DB, Janmey PA, Lind SE: Circulating actin-gelsolin complexes following oleic acid-induced lung injury. Am J Pathol 1988;130:261–267.
  27. Lind SE, Smith DB, Janmey PA, Stossel TP: Depression of gelsolin levels and detection of gelsolin-actin complexes in plasma of patients with acute lung injury. Am Rev Respir Dis 1988;138:429–434.
  28. Suhler E, Lin W, Yin HL, Lee WM: Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis. Crit Care Med 1997;25:594–598.
  29. Osborn TM, Verdrengh M, Stossel TP, Tarkowski A, Bokarewa M: Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis. Arthritis Res Ther 2008;10:R117.
  30. Bucki R, Byfield FJ, Kulakowska A, McCormick ME, Drozdowski W, Namiot Z, Hartung T, Janmey PA: Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components. J Immunol 2008;181:4936–4944.
  31. Cinco M: Selection of a Borrelia burgdorferi antigenic variant by cultivation in the presence of increasing amounts of homologous immune serum. FEMS Microbiol Lett 1992;71:15–18.

  

Author Contacts

Robert Bucki
Institute for Medicine and Engineering, University of Pennsylvania
1010 Vagelos Research Laboratories, 3340 Smith Walk
Philadelphia, PA 19104 (USA)
Tel. +1 215 573 9787, E-Mail buckirob@mail.med.upenn.edu

  

Article Information

Received: September 28, 2010
Accepted after revision: January 13, 2011
Published online: March 10, 2011
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 1, Number of References : 31

  

Publication Details

Neurodegenerative Diseases

Vol. 8, No. 5, Year 2011 (Cover Date: June 2011)

Journal Editor: Nitsch R.M. (Zürich), Hock C. (Zürich)
ISSN: 1660-2854 (Print), eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background/Aims: Cell damage during the course of inflammation results in cytoplasmic actin release, which if not eliminated by the extracellular actin scavenger system, composed of gelsolin and vitamin D binding protein, can cause dysfunction of hemostasis and toxicity towards surrounding cells. In this study, we test the hypothesis that an inflammatory reaction induced by central nervous system infections such as tick-borne encephalitis (TBE) or Lyme neuroborreliosis (LNB) will result in plasma gelsolin concentration changes in the blood and cerebrospinal fluid (CSF). Methods: Quantitative Western blot was used to determine gelsolin levels in 58 samples, which include: 29 patients without infection (diagnosed with conditions such as idiopathic cephalalgia, idiopathic Bell’s facial nerve palsy and ischialgia due to discopathy in which standard CSF diagnostic tests show no abnormalities), 12 patients diagnosed with TBE, and 17 patients diagnosed with LNB sub forma meningitis. Results and Conclusion: The gelsolin concentration in the blood of patients with TBE (163.2 ± 80.8 µg/ml) and LNB (113.6 ± 56.8 µg/ml) was significantly lower (p < 0.05 and p < 0.001, respectively) compared to the control group (226.3 ± 100.7 µg/ml). Furthermore, there was no statistically significant difference between the CSF gelsolin concentration in patients with TBE (3.9 ± 3.3 µg/ml), LNB (2.9 ± 1.2 µg/ml) and the control group (3.7 ± 3.3 µg/ml). An observed decrease in gelsolin concentration in the blood of TBE and LNB patients supports previous findings indicating the involvement of gelsolin in the pathophysiology of an inflammatory response. Therefore, evaluation of blood gelsolin concentration and administration of recombinant plasma gelsolin might provide a new tool to develop diagnostic and therapeutic strategies for TBE and LNB.

© 2011 S. Karger AG, Basel


  

Author Contacts

Robert Bucki
Institute for Medicine and Engineering, University of Pennsylvania
1010 Vagelos Research Laboratories, 3340 Smith Walk
Philadelphia, PA 19104 (USA)
Tel. +1 215 573 9787, E-Mail buckirob@mail.med.upenn.edu

  

Article Information

Received: September 28, 2010
Accepted after revision: January 13, 2011
Published online: March 10, 2011
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 1, Number of References : 31

  

Publication Details

Neurodegenerative Diseases

Vol. 8, No. 5, Year 2011 (Cover Date: June 2011)

Journal Editor: Nitsch R.M. (Zürich), Hock C. (Zürich)
ISSN: 1660-2854 (Print), eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 9/28/2010
Accepted: 1/13/2011
Published online: 3/10/2011
Issue release date: June 2011

Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Osborn TM, Dahlgren C, Hartwig JH, Stossel TP: Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin. Am J Physiol Cell Physiol 2007;292:C1323–C1330.
  2. Bucki R, Kulakowska A, Byfield FJ, Zendzian-Piotrowska M, Baranowski M, Marzec M, Winer JP, Ciccarelli NJ, Gorski J, Drozdowski W, Bittman R, Janmey PA: Plasma gelsolin modulates cellular response to sphingosine-1-phosphate. Am J Physiol Cell Physiol 2010;299:C1516–C1523.
  3. Bucki R, Georges PC, Espinassous Q, Funaki M, Pastore JJ, Chaby R, Janmey PA: Inactivation of endotoxin by human plasma gelsolin. Biochemistry 2005;44:9590–9597.
  4. DiNubile MJ, Stossel TP, Ljunghusen OC, Ferrara JL, Antin JH: Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation. Blood 2002;100:4367–4371.
  5. Lee PS, Waxman AB, Cotich KL, Chung SW, Perrella MA, Stossel TP: Plasma gelsolin is a marker and therapeutic agent in animal sepsis. Crit Care Med 2007;35:849–855.
  6. Rothenbach PA, Dahl B, Schwartz JJ, O’Keefe GE, Yamamoto M, Lee WM, Horton JW, Yin HL, Turnage RH: Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction. J Appl Physiol 2004;96:25–31.
  7. Lee PS, Patel SR, Christiani DC, Bajwa E, Stossel TP, Waxman AB: Plasma gelsolin depletion and circulating actin in sepsis: a pilot study. PLoS One 2008;3:e3712.
  8. Kulakowska A, Drozdowski W, Sadzynski A, Bucki R, Janmey PA: Gelsolin concentration in cerebrospinal fluid from patients with multiple sclerosis and other neurological disorders. Eur J Neurol 2008;15:584–588.
  9. Lee PS, Sampath K, Karumanchi SA, Tamez H, Bhan I, Isakova T, Gutierrez OM, Wolf M, Chang Y, Stossel TP, Thadhani R: Plasma gelsolin and circulating actin correlate with hemodialysis mortality. J Am Soc Nephrol 2009;20:1140–1148.
  10. Hildenbrand P, Craven DE, Jones R, Nemeskal P: Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol 2009;30:1079–1087.
  11. Pachner AR, Steiner I: Lyme neuroborreliosis: infection, immunity, and inflammation. Lancet Neurol 2007;6:544–552.
  12. Fallon BA, Levin ES, Schweitzer PJ, Hardesty D: Inflammation and central nervous system Lyme disease. Neurobiol Dis 2010;37:534–541.
  13. Atrasheuskaya AV, Fredeking TM, Ignatyev GM: Changes in immune parameters and their correction in human cases of tick-borne encephalitis. Clin Exp Immunol 2003;131:148–154.
  14. Gelpi E, Preusser M, Laggner U, Garzuly F, Holzmann H, Heinz FX, Budka H: Inflammatory response in human tick-borne encephalitis: analysis of postmortem brain tissue. J Neurovirol 2006;12:322–327.
  15. Kaiser R: Tick-borne encephalitis. Infect Dis Clin North Am 2008;22:561–575, x.
  16. Mygland A, Ljostad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I: EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol 2010;17:8–16, e11–e14.
  17. Mounzer KC, Moncure M, Smith YR, DiNubile MJ: Relationship of admission plasma gelsolin levels to clinical outcomes in patients after major trauma. Am J Respir Crit Care Med 1999;160:1673–1681.
  18. Nau R, Christen HJ, Eiffert H: Lyme disease – current state of knowledge. Dtsch Arztebl Int 2009;106:72–81, quiz 82, I.
  19. Kwiatkowski DJ, Mehl R, Izumo S, Nadal-Ginard B, Yin HL: Muscle is the major source of plasma gelsolin. J Biol Chem 1988;263:8239–8243.
  20. Mansfield KL, Johnson N, Phipps LP, Stephenson JR, Fooks AR, Solomon T: Tick-borne encephalitis virus – a review of an emerging zoonosis. J Gen Virol 2009;90:1781–1794.
  21. Neuwelt EA: Mechanisms of disease: the blood-brain barrier. Neurosurgery 2004;54:131–140, discussion 141–132.
  22. Lipscomb MF, Masten BJ: Dendritic cells: immune regulators in health and disease. Physiol Rev 2002;82:97–130.
  23. Moretta A, Marcenaro E, Parolini S, Ferlazzo G, Moretta L: NK cells at the interface between innate and adaptive immunity. Cell Death Differ 2008;15:226–233.
  24. Aravalli RN, Peterson PK, Lokensgard JR: Toll-like receptors in defense and damage of the central nervous system. J Neuroimmune Pharmacol 2007;2:297–312.
  25. Bucki R, Levental I, Kulakowska A, Janmey PA: Plasma gelsolin: function, prognostic value, and potential therapeutic use. Curr Protein Pept Sci 2008;9:541–551.
  26. Smith DB, Janmey PA, Lind SE: Circulating actin-gelsolin complexes following oleic acid-induced lung injury. Am J Pathol 1988;130:261–267.
  27. Lind SE, Smith DB, Janmey PA, Stossel TP: Depression of gelsolin levels and detection of gelsolin-actin complexes in plasma of patients with acute lung injury. Am Rev Respir Dis 1988;138:429–434.
  28. Suhler E, Lin W, Yin HL, Lee WM: Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis. Crit Care Med 1997;25:594–598.
  29. Osborn TM, Verdrengh M, Stossel TP, Tarkowski A, Bokarewa M: Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis. Arthritis Res Ther 2008;10:R117.
  30. Bucki R, Byfield FJ, Kulakowska A, McCormick ME, Drozdowski W, Namiot Z, Hartung T, Janmey PA: Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components. J Immunol 2008;181:4936–4944.
  31. Cinco M: Selection of a Borrelia burgdorferi antigenic variant by cultivation in the presence of increasing amounts of homologous immune serum. FEMS Microbiol Lett 1992;71:15–18.