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Effect of intra-erythrocytic magnesium ions on invasion by Plasmodium falciparum
S J Field1, K Rangachari, A R Dluzewski
1Medical Research Council Muscle and Cell Motility Unit, King's College, London.
Abstract:
Exclusion of magnesium ions from resealed ghosts or their extraction from intact human red cells by means of an ionophore results in a reversible drop in susceptibility to invasion by Plasmodium falciparum merozoites in vitro. Resealed ghosts, containing magnesium-ATP and diluted cytosol, are invaded with high efficiency only when the original hypotonic lysis is carried out in the presence of magnesium ions. This effect is not related to the loss of membrane-associated constituents when magnesium ions are absent. Ghosts containing calcium ions, together with the protective agent, flunarizine, were essentially resistant to invasion; this effect is again at least partially reversible. A possible explanation of these phenomena is that entry of the merozoite may be inhibited by breakdown of the host cell phospholipid asymmetry, with the appearance of aminophospholipids at the outer cell surface.
Insights
Magnesium ions are crucial for human red blood cell invasion by Plasmodium falciparum merozoites. Removing magnesium ions reversibly reduces parasite invasion, suggesting a role in host cell vulnerability.
Area of Science:
- Cell Biology
- Parasitology
- Biochemistry
Background:
- Plasmodium falciparum merozoites infect human red blood cells, causing malaria.
- The mechanisms governing red blood cell susceptibility to merozoite invasion are not fully understood.
- Ion concentrations within red blood cells may play a role in parasite invasion.
Purpose of the Study:
- To investigate the role of magnesium ions in Plasmodium falciparum merozoite invasion of human red blood cells.
- To explore the effects of calcium ions and flunarizine on red blood cell invasion susceptibility.
Main Methods:
- Used resealed human red blood cell ghosts and intact red cells.
- Manipulated intracellular magnesium and calcium ion concentrations using ionophores and hypotonic lysis.
- Assessed merozoite invasion efficiency in vitro.
Main Results:
- Exclusion or extraction of magnesium ions significantly reduced red blood cell invasion by P. falciparum merozoites.
- Magnesium-ATP and cytosol were necessary for efficient invasion in resealed ghosts.
- Ghosts with calcium ions and flunarizine showed resistance to invasion, which was partially reversible.
Conclusions:
- Magnesium ions are essential for efficient invasion of human red blood cells by Plasmodium falciparum.
- The invasion process may be linked to the maintenance of red blood cell phospholipid asymmetry.
- Disruption of phospholipid asymmetry, indicated by externalized aminophospholipids, may inhibit merozoite entry.