PHILADELPHIA - One of the world's most devastating diseases is malaria, responsible for at least a million deaths annually, despite global efforts to combat it. Researchers from the Perelman School of Medicine at the University of Pennsylvania, working with collaborators from Drexel University, The Children's Hospital of Philadelphia, and Johns Hopkins University, have identified a protein in human blood platelets that points to a powerful new weapon against the disease. Their work was published in this months' issue of Cell Host and Microbe.
Malaria is caused by parasitic microorganisms of the Plasmodium genus, which infect red blood cells. Recent research at other universities showed that blood platelets can bind to infected red blood cells and kill the parasite, but the exact mechanism was unclear. The investigators on the Cell Host and Microbe paper hypothesized that it might involve host defense peptides (HDP) secreted by the platelets.
"We eventually found that a single protein secreted when platelets are activated called human platelet factor 4 [hPF4] actually kills parasites that are inside red cells without harming the red cell itself," explains senior author Doron Greenbaum, PhD, assistant professor of Pharmacology, whose team studies innovative ways to fight malaria. The hPF4 targets a specific organelle of the Plasmodium falciparum parasite called the digestive vacuole, which essentially serves as its "stomach" for the digestion of hemoglobin. The investigators found that hPF4 destroys the vacuole with a deadly speed of minutes or even seconds, killing the parasite without affecting the host cell.
While host defense peptides appear to be attractive therapeutic agents, the expense of manufacturing this protein lessens its potential impact on the treatment of malaria. Greenbaum and colleagues set out to discover whether synthetic molecules mimicking the structure of HDPs could have simi
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine