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Plasmodium falciparum is the most dangerous of the various malaria pathogens and, if left untreated, leads to severe, life-threatening disease progression. The malaria pathogen is a parasite and infects red blood cells (erythrocytes). These bind to the walls of small blood vessels and can damage important organs, such as the kidneys, lungs or brain, through lack of oxygen and overactivation of the immune system. The research group led by Prof. Iris Bruchhaus at the Bernhard Nocht Institute of Tropical Medicine (BNITM) has deciphered the complex processes that occur during the interaction of infected erythrocytes with different receptors of the blood vessel walls. The results of this work were recently published in the journal Scientific Reports.
In their study, Dr. Nahla Galal Metwally and Dr. Pedro Lubiana from Bruchhaus' group analysed how strongly erythrocytes infected with malaria parasites bind to different receptors of the vascular walls. They simulated different flow velocities as well as elevated temperatures (similar to febrile conditions). In order to determine the strength of the binding, the group used a special method, the so-called "laminar flow system". This system imitates the hydrodynamic forces acting on infected erythrocytes under flow conditions in the blood vessels. "In all experiments, we generated different shear stresses similar to those acting on infected erythrocytes on the walls of human blood vessel," explains Metwally.
The scientists combined the laminar flow system with another new bioinformatics method and thus characterised the dynamics of the binding between erythrocytes and different receptors of the vessel walls. "Our research results clearly highlight the complexity of the interaction between the surface molecules of infected erythrocytes and the receptors of the blood vessel walls," said group leader Bruchhaus explaining the results. Infected erythrocytes first bind to the CD36 receptor and slowly roll over the vascular walls.
This rolling stimulates the cells of the vascular wall, which then form further receptors and transport them to the vessel surfaces. This leads to a very stable binding of the infected erythrocytes to the vessel walls.
At elevated, fever-like temperatures, it is also important for the malaria parasite to form certain structures on the surface of the infected erythrocytes, the so-called "knobs", so that they can remain longer on the vessel wall. Understanding the complex interactions between parasite-infected erythrocytes and the receptors of the blood vessel walls opens up new possibilities: "New targeted approaches for the improved treatment and control of malaria are thus conceivable," emphasises Bruchhaus.