The effects of chemical modification on the adhesion of Plasmodium falciparum-infected and uninfected erythrocytes

Binding of Plasmodium falciparum-infected erythrocytes (PE) to endothelial cells is mediated by the erythrocyte-membrane protein, band 3-related adhes in. To determine its role, the binding of infected cells treated with vario us chemical modifiers was investigated. Binding was inhibited by a lysine m odifier (1,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)) known to spec ifically bind to band 3, another lysine modifier (trinitrobenzene sulfonic acid), a tyrosine modifier (sodium iodide in conjunction with lactoperoxida se, hydrogen peroxide) and oxidants (diamide, sodium periodate and ADP-chel ated ferric ion), but binding was unaffected by the histidine modifier (die thylpyrocarbonate) and the arginine modifier (phenyl glyoxyl monohydrate). To artificially expose the band 3-related adhesin, uninfected erythrocytes were treated with acridine orange or loaded with calcium. These cells bound to C32 amelanotic melanoma cells, were immunostained with a monoclonal ant ibody that specifically binds to the band 3-related adhesin on PE, and the binding was inhibited by this monoclonal antibody. The binding of acridine orange-treated and calcium-loaded uninfected erythrocytes, could also be bl ocked by DIDS. In the case of acridine orange-treated erythrocytes, the pat terns of the effects of the chemical modification on binding were consisten t with that of PE except for tyrosine modification. These results demonstra te that the band S-related adhesin, even in the absence of parasite-encoded proteins, contributes to PE adhesion.