Control of malaria virulence by alpha 1-acid glycoprotein (orosomucoid), an acute-phase (inflammatory) reactant.

During malaria and other infections, the plasma concentration of alpha 1-acid glycoprotein (AGP) increases 3- to 4-fold, but the function of this glycoprotein has been unknown. This study demonstrates, by in vitro culture of the malaria parasite Plasmodium falciparum, that the AGP concentration achieved during malaria is sufficient to inhibit parasite multiplication by 80%. It was found that the inhibitory activity of AGP depends on and is a function of its sialic acid complement (12-16 mol/mol) and its higher-order structure. AGP acts by blocking parasite-erythrocyte interaction during the invasion process. These findings indicate a function for AGP with definite in vivo significance. Moreover, they reveal an important protective response to malaria and perhaps other infectious diseases.