HNE produced by the malaria parasite Plasmodium falciparum generates HNE-protein adducts and decreases erythrocyte deformability.
In Plasmodium falciparum-parasitized erythrocytes, hemozoin (HZ) formation was accompanied by enhanced formation of 4-hydroxynonenal (HNE)-protein adducts on the cell surface, reaching in the HZ-rich schizont forms the 16.8-fold amount of control non-parasitized cells. The addition of 1-100 microM exogenous HNE to control non-parasitized cells generated HNE-adducts on surface proteins in amounts similar to those found in schizonts. Parasitized as well as HNE-treated non-parasitized erythrocytes showed decreased cell deformability (measured as decreased filterability through cylindrical-pore filters) related to the amount of HNE adducts. In vivo, the HZ-containing trophozoites and schizonts are phagocytic targets for monocytes/macrophages. The reduced deformability of circulating erythrocytes carrying HNE-adducts may increase their phagocytic elimination. Uncontrolled HNE production by parasitized erythrocytes may additionally modify non-parasitized bystander erythrocytes, induce their phagocytosis, and contribute to malarial anemia, which is predominantly due to the removal of large numbers of indirectly damaged non-parasitized erythrocytes.
Skorokhod
Aleksei
A
Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Torino, Italy.
Schwarzer
Evelin
E
Gremo
Giuliana
G
Arese
Paolo
P
D000447:Aldehydes / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004907:Erythrocyte Deformability / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology*; D006420:Hemeproteins / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000469:parasitology / Q000502:physiology; D009000:Monocytes / Q000469:parasitology / Q000502:physiology; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000472:pathogenicity*
D000447:Aldehydes; D001798:Blood Proteins; D006420:Hemeproteins; C020753:hemozoin; C027576:4-hydroxy-2-nonenal