Calcium and the malaria parasite: parasite maturation and the loss of red cell deformability.
In the studies reported here, we examined the role of calcium in the maturation of the human malaria parasite Plasmodium falciparum, and in the loss of red cell deformability associated with parasite maturation. P. falciparum alters the permeability of its host red cell, which normally maintains submicromolar cytoplasmic concentrations of calcium. Infection of the red cell and parasite maturation produce a 30-fold increase in calcium uptake. Both parasite maturation and the loss of red cell deformability are blocked by EGTA (by extracellular-free calcium concentrations less than or equal to 35 microM) and by other calcium antagonists. The loss of red cell deformability that occurs with parasite maturation is accompanied by alterations in the cytoskeletal proteins of parasitized red cells similar to those produced by the calcium ionophore A23187 (reductions in bands 2.1 [ankyrin], 4.1, and 5 [actin]). These results establish that parasite development and the loss of red cell deformability are calcium-dependent. They suggest that parasite-induced changes in the calcium permeability of the red cell activate endogenous transglutaminase activity by raising the free calcium concentration of the red cell cytoplasm.
Krogstad
D J
DJ
Department of Medicine, Washington University, St. Louis, Missouri 63110.
Sutera
S P
SP
Marvel
J S
JS
Gluzman
I Y
IY
Boylan
C W
CW
Colca
J R
JR
Williamson
J R
JR
Schlesinger
P H
PH
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D002132:Calcium Radioisotopes; D003598:Cytoskeletal Proteins / Q000097:blood; D004533:Egtazic Acid / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*
D002132:Calcium Radioisotopes; D003598:Cytoskeletal Proteins; D000001:Calcimycin; D004533:Egtazic Acid; D002118:Calcium