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Glycosylphosphatidylinositol-induced cardiac myocyte death might contribute to the fatal outcome of Plasmodium falciparum malaria

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Abstract

Background

Glycosylphosphatidylinositol (GPI) purified from Plasmodium falciparum has been shown to play an important role as a toxin in the pathology of malaria. Previous studies demonstrated cardiac involvement in patients suffering from severe malaria due to P. falciparum. Therefore, we tested the hypothesis that GPI induces apoptosis in cardiomyocytes.

Methods and results

By using TUNEL and caspase activity assays, we provided evidence for apoptosis induction in cardiomyocytes by P. falciparum GPI after 48 h of incubation. A similar result was obtained in heart cells of mice 48 h after in vivo injection of GPI. Gene expression analyses in GPI-treated cardiomyocytes showed an up-regulation of apoptotic genes (apaf-1, bax) and of a myocardial damage marker bnp (brain natriuretic peptide), while a down-regulation was observed for the anti-apoptotic gene bcl-2 and for the heat shock protein hsp70. In spite of inflammatory cytokine gene up-regulation by GPI, co-culture with peripheral mononuclear cells (PMNCs) did not change the results obtained with cardiomyocytes alone, indicating a direct effect of GPI on cardiac myocytes. Co-culture with non-myocytic cardiac cells (NMCCs) resulted in up-regulation of Hsp70 and Bcl-2 genes in GPI-treated cardiomyocytes but without repercussion on the apoptosis level. A malaria-infected patient, presenting fulminant heart failure showed typical signs of cardiac myocyte apoptosis demonstrating the clinical relevance of toxin induced heart damage for the lethality of malaria. Our studies performed in vitro and in mice suggest that the GPI could be responsible for cardiomyocyte apoptosis that occurred in this patient.

Conclusion

Plasmodium falciparum GPI-induced apoptosis might participate in the lethality of malaria.

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Notes

  1. Man = mannose

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Department of Internal Medicine – Cardiology, Philipps-University of Marburg, University Hospital, Baldingerstrasse 1, 35043, Marburg/Lahn, Germany

    Kathrin Wennicke, Sabine Pankuweit, Bernhard Maisch & Volker Ruppert

  2. Laboratory of Parasitology, Institute of Virology, Philipps-University Marburg, Marburg, Germany

    Françoise Debierre-Grockiego & Ralph T. Schwarz

  3. I. Medical Department, Infectious Diseases and Tropical Medicine Section, University Hospital Hamburg Eppendorf, Hamburg, Germany

    Dominic Wichmann

  4. Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany

    Norbert W. Brattig

  5. UMR CNRS/USTL 8576, Unité de Glycobiologie Structurale et Fonctionnelle, Villeneuve D’Ascq, France

    Ralph T. Schwarz

Authors
  1. Kathrin Wennicke
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  2. Françoise Debierre-Grockiego
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  3. Dominic Wichmann
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  4. Norbert W. Brattig
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  5. Sabine Pankuweit
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  6. Bernhard Maisch
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  7. Ralph T. Schwarz
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  8. Volker Ruppert
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Corresponding author

Correspondence to Volker Ruppert.

Additional information

Kathrin Wennicke and Françoise Debierre-Grockiego contributed equally to this work.

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Wennicke, K., Debierre-Grockiego, F., Wichmann, D. et al. Glycosylphosphatidylinositol-induced cardiac myocyte death might contribute to the fatal outcome of Plasmodium falciparum malaria. Apoptosis 13, 857–866 (2008). https://doi.org/10.1007/s10495-008-0217-6

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  • DOI: https://doi.org/10.1007/s10495-008-0217-6

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