Inhibition of malarial invasion of red cells by chemical and immunochemical linking of spectrin molecules.

The invasion of resealed human red cell ghosts by Plasmodium falciparum, and those from monkey cells by P. knowlesi, was strongly inhibited by anti-spectrin antibodies introduced into their cytoplasm. Univalent F(ab)1 fragments gave no such effect, but a combination of these fragments and goat anti-rabbit immunoglobulin, to restore bifunctionality, caused perceptible inhibition of invasion. Disulphide cross-links introduced between spectrin molecules in intact red cells by the membrane-permeant oxidizing agent, diamide, again led to inhibition of invasion. This effect was largely reversed by reduction of the cross-links. Gel electrophoresis was used to confirm that cross-linking was essentially confined to spectrin, and that extended covalent networks were not formed. It follows that local formation of bridges, whether by antibodies or oxidation of thiol groups, functions by inhibiting a local rearrangement of the cytoskeleton that forms a step in the invasion process.