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Original Article

Ramachandra S. Naik^a, OraLee H. Branch^b, Amina S. Woods^c, Matam Vijaykumar^a, Douglas J. Perkins^b, Bernard L. Nahlen^b,e, Altaf A. Lal^b, Robert J. Cotter^c, Catherine E. Costello^f, Christian F. Ockenhouse^d, Eugene A. Davidson^a, and D. Channe Gowda^a

^a Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007
^b Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341
^c Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
^d Walter Reed Army Institute of Research, Silver Spring, Maryland 20910
^e Vector Biology and Control Center, Kenya Medical Research Institute, Kisumu, Kenya
^f Mass Spectrometry Resource, Boston University School of Medicine, Boston, Massachusetts 02118
Department of Biochemistry and Molecular Biology, 3900 Reservoir Rd., N.W., Washington, DC 20007.202-687-7186202-687-3840

gowda{at}bc.georgetown.edu

Induction of proinflammatory cytokine responses by glycosylphosphatidylinositols (GPIs) of intraerythrocytic Plasmodium falciparum is believed to contribute to malaria pathogenesis. In this study, we purified the GPIs of P. falciparum to homogeneity and determined their structures by biochemical degradations and mass spectrometry. The parasite GPIs differ from those of the host in that they contain palmitic (major) and myristic (minor) acids at C-2 of inositol, predominantly C18:0 and C18:1 at sn-1 and sn-2, respectively, and do not contain additional phosphoethanolamine substitution in their core glycan structures. The purified parasite GPIs can induce tumor necrosis factor release from macrophages. We also report a new finding that adults who have resistance to clinical malaria contain high levels of persistent anti-GPI antibodies, whereas susceptible children lack or have low levels of short-lived antibody response. Individuals who were not exposed to the malaria parasite completely lack anti-GPI antibodies. Absence of a persistent anti-GPI antibody response correlated with malaria-specific anemia and fever, suggesting that anti-GPI antibodies provide protection against clinical malaria. The antibodies are mainly directed against the acylated phosphoinositol portion of GPIs. These results are likely to be valuable in studies aimed at the evaluation of chemically defined structures for toxicity versus immunogenicity with implications for the development of GPI-based therapies or vaccines.

Key Words: malaria parasite • cytokine response • antigenicity • acquired immunity • pathogenesis

R.S. Naik, O.H. Branch, and A.S. Woods contributed equally to this work.

D.J. Perkins is also associated with the Division of Hematology, Duke University Department of Medicine, Durham, NC 27705.

© 2000 The Rockefeller University Press

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