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Science 301 (5640): 1734-1736

Copyright © 2003 by the American Association for the Advancement of Science

Erythrocyte G Protein-Coupled Receptor Signaling in Malarial Infection

Travis Harrison,1,2 Benjamin U. Samuel,1,2* Thomas Akompong,1,2 Heidi Hamm,3 Narla Mohandas,4 Jon W. Lomasney,1{dagger} Kasturi Haldar1,2{dagger}

Abstract: Erythrocytic mechanisms involved in malarial infection are poorly understood. We have found that signaling via the erythrocyte ß2-adrenergic receptor and heterotrimeric guanine nucleotide–binding protein (G{alpha}s) regulated the entry of the human malaria parasite Plasmodium falciparum. Agonists that stimulate cyclic adenosine 3',5'-monophosphate production led to an increase in malarial infection that could be blocked by specific receptor antagonists. Moreover, peptides designed to inhibit G{alpha}s protein function reduced parasitemia in P. falciparum cultures in vitro, and ß-antagonists reduced parasitemia of P. berghei infections in an in vivo mouse model. Thus, signaling via the erythrocyte ß2-adrenergic receptor and G{alpha}s may regulate malarial infection across parasite species.

1 Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 Chicago Avenue, Chicago, IL 60611, USA.
2 Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 Chicago Avenue, Chicago, IL 60611, USA.
3 Department of Pharmacology, Vanderbilt University, Nashville, TN 37240, USA.
4 New York Blood Center, New York, NY 10021, USA.

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* Present address: Department of Ophthalmology and Visual Sciences, University of Chicago, Room 103 Visual Science Center, Chicago, IL 60637, USA.

{dagger} To whom correspondence should be addressed. E-mail: k-haldar{at}northwestern.edu (K.H.); j-lomasney{at}northwestern.edu (J.W.L.)

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