Oxidation of hemoglobin and redistribution of band 3 promote erythrophagocytosis in visceral leishmaniasis

In visceral leishmaniasis (VL), oxidative assault on erythrocytes perturbs their cellular environment and makes them vulnerable to premature hemolysis. In this study, we assessed the contribution of oxidation-induced modifications of hemoglobin and membrane protein band 3 in the reduced survival of red cells in VL. Oxidative transformation of oxyhemoglobin to hemichrome enhanced its interaction with erythrocyte membrane in the infected animals. Association between denatured globin and band 3 contributed to the formation of insoluble copolymer of macromolecular dimension. Disulfide bonding appeared to be necessary in the making of high molecular weight aggregates during copolymerization. Hemichrome induced clustering of band 3 promoted generation of epitopes on erythrocyte cell surface. This provided a signal favoring immunologic recognition of redistributed band 3 by autologous IgG followed by erythrophagocytosis. An eventual outcome of the sequence of events pointed to early removal of affected red cells from circulation during the disease