Growth of Plasmodium falciparum in human erythrocytes containing abnormal membrane proteins.
To evaluate the role of erythrocyte (RBC) membrane proteins in the invasion and maturation of Plasmodium falciparum, we have studied, in culture, abnormal RBCs containing quantitative or qualitative membrane protein defects. These defects included hereditary spherocytosis (HS) due to decreases in the content of spectrin [HS(Sp+)], hereditary elliptocytosis (HE) due to protein 4.1 deficiency [HE(4.1(0))], HE due to a spectrin alpha I domain structural variant that results in increased content of spectrin dimers [HE(Sp alpha I/65)], and band 3 structural variants. Parasite invasion, measured by the initial uptake of [3H]hypoxanthine 18 hr after inoculation with merozoites, was normal in all of the pathologic RBCs. In contrast, RBCs from six HS(Sp+) subjects showed marked growth inhibition that became apparent after the first or second growth cycle. Preincubation of HS(Sp+) RBCs in culture for 3 days did not alter these results. Normal parasite growth was observed in RBCs from one HS subject with normal membrane spectrin content. The extent of decreased parasite growth in HS(Sp+) RBCs closely correlated with the extent of RBC spectrin deficiency (r = 0.90). Homogeneous subpopulations of dense HS RBCs exhibited decreased parasite growth to the same extent as did HS whole blood. RBCs from four HE subjects showed marked parasite growth inhibition, the extent of which correlated with the content of spectrin dimers (r = 0.94). RBCs from two unrelated subjects with structural variants of band 3 sustained normal parasite growth. Decreased growth in the pathologic RBCs was not the result of decreased ATP or glutathione levels or of increased RBC hemolysis. We conclude that abnormal parasite growth in these RBCs is not the consequence of metabolic or secondary defects. Instead, we suggest that a functionally and structurally normal host membrane is indispensable for parasite growth and development.
Division of Hematology, Albert Einstein College of Medicine, Bronx, NY.
S
S
Schulman
E F
EF
Roth
B
B
Cheng
A C
AC
Rybicki
I I
II
Sussman
M
M
Wong
W
W
Wang
H M
HM
Ranney
R L
RL
Nagel
R S
RS
Schwartz
D000818:Animals; D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000097:blood* / Q000502:physiology; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000472:pathogenicity; D013049:Spectrin / Q000235:genetics* / Q000502:physiology; D013103:Spherocytosis, Hereditary / Q000097:blood*
D008565:Membrane Proteins; D013049:Spectrin