Tuesday, April 23, 2013

The Role of Platelets in Defense against Malaria

Platelets are normal constituents of the blood.  They play a fundamental role in blood clotting, but have been shown to play other more diverse functions.  For example, it has been well established that platelets impede the growth of the malaria parasite, Plasmodium falciparum.  The malaria parasite enters the bloodstream following the bite of its carrier, the female anopheles mosquito.  Once circulating in the bloodstream, the parasite preferentially invades circulating red blood cells.  Platelets bind to parasitized cells and kill the parasites within.  This has been amply demonstrated in studies with mice – normally resistant to infection – that have been purposefully depleted of platelets.  These mice invariably die of infection.  It has also been shown, that this property of platelets is independent of species – platelets derived from mice or humans exert the same effect in either host.  In addition, platelets seemed to bind to both infected and non-infected cells, but have a marked preference for infected red cells. 

Although this capability of platelets has been well established, the actual molecular mechanism underlying this function has not been fully demonstrated.  Dr. Brendan J. McMorran and his colleagues from the Australian School of Advanced Medicine in Macquarie University, Sydney Australia and the Menzies Research Institute Tasmania University, Hobart, Australia have made a significant contribution to the understanding of the mechanism involved.

From their work, they have shown that platelet factor 4 (PF4) together with the Duffy-antigen receptor (Fy) are necessary for the platelet-mediated eradication of the Plasmodium falciparum parasite.  Furthermore, they have shown that upon the binding of platelets to the parasitized red blood cell, PF4 is released and that it is this protein that is responsible for the killing of the parasites residing within the infected red blood cells.  In order for PF4 to exert its effect, Fy needs to be present; it is Fy that selectively binds to PF4.  It has also been shown that those individuals that have a genetic anomaly that undermines the expression of Fy are devoid of the protection against the parasite provided by platelets.

These findings help to elucidate the role that platelets play in the defense against parasitic infections.  Uncovering the underlying mechanism for such a defense may prove to be invaluable in combating malaria - a disease that has a devastating impact on a significant portion of the world’s population.    

No comments:

Post a Comment