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

作者:Wennicke Kathrin; Debierre Grockiego Francoise; Wichmann Dominic; Brattig Norbert W; Pankuweit Sabine; Maisch Bernhard; Schwarz Ralph T; Ruppert Volker*
来源:Apoptosis, 2008, 13(7): 857-866.
DOI:10.1007/s10495-008-0217-6

摘要

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 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.

  • 出版日期2008-7