Abstract
Invasion of red cells by Plasmodium falciparum in vitro was inhibited by a range of extracellular ligands, none of which block the major receptors for merozoites. Most effective, in terms of dose response, were two monoclonal antibodies against the Wrb antigen on glycophorin A; wheat germ agglutinin which also binds to glycophorin, and an anti-band 3 monoclonal antibody, caused inhibition of invasion at higher levels of saturation, while binds to band 3, was without effect. All the ligands except concanavalin A, increased the rigidity of the host cell membrane. The anti-Wrb antibodies generated the highest dose response effect, but no correlation between invasion and shear elastic modulus of the membrane could be established. All ligands, with the exception of concanavalin A, caused a reduction in the translationally mobile fractions of band 3 and glycophorin, as revealed by fluorescence recovery after photobleaching (FRAP). Invasion diminished with loss of mobile band 3, engendered by bound wheat germ agglutinin or anti-band 3, falling precipitately when the mobile fraction fell below 40% of that in unperturbed membranes. Both anti-Wrb antibodies suppressed invasion completely at concentrations insufficient to affect significantly either membrane rigidity or intramembrane protein diffusion. A univalent anti-glycophorin A (Fab) fragment, the parent antibody of which was previously shown to inhibit invasion strongly, had only a modest effect on invasion and induced a correspondingly small change in the mobile fraction of band 3. We conjecture that inhibition of migration of intramembrane proteins may oppose invasion by preventing formation of a bare zone in the host cell membrane, but antibodies against the Wrb determinant prevent invasion by an additional and overriding mechanism, related perhaps to transmission of a structural transmembrane signal, which could uncouple the reciprocal movement of intramembrane proteins and the spectrin network, or to formation of band 3-glycophorin A-antibody clusters.
Original language | English |
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Pages (from-to) | 19-27 |
Number of pages | 9 |
Journal | Molecular and biochemical parasitology |
Volume | 69 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 1995 |
Bibliographical note
Funding Information:We arei ndebtedto Dr. E. Zintzaras(N .1.M.R)f or statisticael valuationo f the diffusiond ata.T his work was supportedb y the UNDP/World Bank/World Health OrganizationS pecial Programmef or Re-searcha ndT rainingi n TropicalD iseases.
Keywords
- Band 3
- Glycophorin A
- Invasion
- Malaria
- Red cell membrane
ASJC Scopus subject areas
- Parasitology
- Molecular Biology