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what is necessary for platelet mediated killing of malaria parasite?
- 1. Platelet molecule platelet factor 4 (PF4 or CXCL4)
- 2. Duffy-antigen receptor (Fy)
How do platelets work to mediate malaria parasites
RESTRICT GROWTH by binding to parasitized cells and KILLING parasite inside
Function of PF4 and Fy in killing parasites
- PF4 comes into contact with the parasitized cell and this protein directly kills the internal parasite.
- PF4 utilizes Fy, which BINDS to PF4. If NO Fy binding, then PF4 CANNOT kill the parasite
Cooperative effect in production of PF4 by Fy
PF4 that binds to Fy may mediate the increase in PF4 concentration on cell surface
If you do not have Fy…
- You prevent parasite killing
- PF4 or platelets are NOT able to prevent growth of P falciparum parasites
Experiments used to ID dead intraerythrocytic parasites and results
- TUNEL assay used
- +PF4 (platelet treatment) showed INCREASE in dead parasites vs cells without PF4
- rhPF4 treatment at different stages of parasitic development showed PF4 preferentially kills at LATER STAGES of parasitic development