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Am. J. Trop. Med. Hyg., 34(2), 1985, pp. 223-227
Copyright © 1985 by The American Society of Tropical Medicine and Hygiene

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Toxic Heme in Sickle Cells: an Explanation for Death of Malaria Parasites*

Augustine U. Orjih{dagger}, Rekha Chevli AND Coy D. Fitch
Department of Internal Medicine, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, Missouri 63104

In an effort to elucidate a mechanism of genetic resistance to malaria, we asked whether a toxic form of heme is included in the excess of ferriprotoporphyrin IX (FP) which has been reported to accumulate as hemichromes in sickle cells. When FP is bound to certain erythrocytic elements, such as native hemoglobin, it is inaccessible to bind chloroquine with high affinity and is nontoxic. However, when FP is accessible to bind chloroquine with high affinity, it has been demonstrated to be sufficiently free to have membrane toxicity and, under certain conditions, to lyse Plasmodium falciparum parasites. [14C]-chloroquine was used, therefore, as a reporter molecule to evaluate the quantity, accessibility, and potential toxicity of FP released from hemoglobin. Intact erythrocytes from subjects with sickle cell anemia bound approximately 71 µmoles of chloroquine per kg with an apparent Kd of 10-6 M. Erythrocytes from normal subjects or subjects with sickle trait bound little or no chloroquine with high affinity. Since the oxidant stress introduced by malaria parasites would increase the tendency for denaturation of hemoglobin S with additional release of FP, we suggest that FP toxicity accounts for the death of malaria parasites in sickle cells.

Accepted for publication October 30, 1984.


* Address reprint requests to: Coy D. Fitch, M.D., Department of Internal Medicine, St. Louis University School of Medicine, 1402 S. Grand Boulevard (M239), St. Louis, Missouri 63104.


{dagger} Visiting Fulbright Scholar. Permanent address: Department of Microbiology, University of Port Harcourt, Port Harcourt, Nigeria.






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Copyright © 1985 by the American Society of Tropical Medicine and Hygiene.