Plasmodium falciparum glycosylphosphatidylinositol induces limited apoptosis in liver and spleen mouse tissue

Abstract

Plasmodium falciparum malaria affects about 500 million people worldwide and is responsible for approximately 2.5 million deaths per year. Glycosylphosphatidylinositol (GPI) is the major anchor for membrane-associated proteins of P. falciparum and GPI plays a major role as a toxin in the pathology of malaria. Therefore, we tested the Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.hypothesis that GPI, like LPS, induces apoptosis in vitro and in vital organs of mice. Our data does not provide evidence for direct cardiomyocyte apoptosis induced by GPI in vitro. However, in vivo injection of GPI induced limited apoptosis in mouse liver and spleen tissue. Apoptosis may be due to a direct GPI apoptotic effect or to an indirect effect via the induction of TNFα and nitric oxide production.

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

“…Our data provide no evidence for an apoptosis induction in cardiomyocytes after 24 h of GPI stimulation. These results coincide with our data shown before, where we could not find any apoptosis in mouse hearts 24 and 36 h after in vivo injection of GPI [13]. However, after 48 h of incubation we detected apoptosis in cardiomyocytes due to P. falciparum GPI exposure in vitro.…”

“…The cells were treated with GPI from P. falciparum, and apoptosis was determined by the detection of specific DNA strand breaks using TUNEL assay. As previously shown [13], incubation during 24 h with GPI of P. falciparum did not lead to a significant increase of cardiomyocyte apoptosis ( Fig. 1a) but, interestingly, GPI strongly increased the percentage of apoptotic cardiomyocytes after 48 h incubation ( Fig.…”

“…3), correlating with the results obtained in vitro. We have previously found that GPI induces apoptosis in spleen and liver tissue after 24 h in vivo injection [13]. Here we show that the GPI apoptotic effect in spleen and liver was still to be seen at 48 h (Fig.…”

“…2b) in rat cardiomyocytes. Our previous study showed the absence of apoptosis in mouse heart tissue 24 h after in vivo injection of GPI [13]. The novel finding that P. falciparum GPI induces cardiomyocyte apoptosis after 48 h in vitro suggests that an apoptotic effect might be visible in vivo 2 days after injection.…”

“…We have previously described that GPI purified from P. falciparum induces apoptosis in the liver and the spleen of mice [13]. Thus, P. falciparum GPI might contribute to the myocardial impairment in severe malaria.…”