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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-10-3105.
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Blood, 15 April 2003, Vol. 101, No. 8, pp. 3309-3315
RED CELLS
Aberrant development of Plasmodium falciparum in
hemoglobin CC red cells: implications for the malaria protective effect
of the homozygous state
Rick M. Fairhurst,
Hisashi Fujioka,
Karen Hayton,
Kathleen F. Collins, and
Thomas
E. Wellems
From the Laboratory of Malaria and Vector Research,
National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health, Bethesda, MD; and Institute of Pathology, Case
Western Reserve University, Cleveland, OH.
Although selection of hemoglobin C (HbC) by malaria has been
speculated for decades, only recently have epidemiologic studies provided support for HbC protection against malaria in West Africa. A
reduced risk of malaria associated with the homozygous CC state has
been attributed to the inability of CC cells to support parasite multiplication in vitro. However, there have been conflicting data and
conclusions regarding the ability of CC red cells to support parasite
replication. Reports that parasites cannot multiply in CC cells in
vitro contrast with detection of substantial parasite densities in CC
patients with malaria. We have therefore investigated Plasmodium
falciparum growth in CC cells in vitro. Our data show that the
multiplication rate of several P falciparum lines is measurable in CC cells, but lower than that in AA (HbA-normal) cells. A
high proportion of ring forms and trophozoites disintegrates within a
subset of CC cells, an observation that accounts for the overall lower
replication rate. In addition, knobs present on the surface of infected
CC cells are fewer in number and morphologically aberrant when compared
with those on AA cells. Events in malaria pathogenesis that involve
remodeling of the erythrocyte surface and the display of parasite
antigens may be affected by these knob abnormalities. Our data suggest
that only a subset of CC cells supports normal parasite replication and
that components of malaria protection associated with the CC state may
affect the parasite's replication capacity and involve aberrant knob formation on CC cells.

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