Altered calcium homeostasis and membrane destabilization in erythrocytes of hamsters infected with Leishmania donovani

Homeostatic mechanisms regulating intracellular concentrations of Ca2+ at a low level are prerequisites for maintaining the integral and cytoskeletal structure of erythrocytes under normal physiological conditions. The presen t study was undertaken to assess the contribution of Ca2+ homeostasis in mo difying red-cell stability in hamsters, during the anaemia caused by Leishm ania donovani. Erythrocytes from the infected animals became increasingly f ragile as infection progressed. This fragility may be the result of a gradu al change in membrane permeability, as indicated by enhanced uptake of Ca-4 5(2+). The increase in cytosolic Ca2+ and decrease in membrane-bound Ca2+ o bserved indicate the release of Ca2+ from the membrane store, leading to [C a2+](i) accumulation in the later stages of the post-infection period. Decl ine in the efficacy of Ca2+-effluxing enzyme may also contribute to the enh anced Ca2+](i) level, with subsequent degradation of membrane proteins in t he erythrocytes of the infected animals. Marked inhibition of proteolytic d egradation by the Ca2+-dependent thiol protease inhibitor leupeptin, with c oncomitant thiol depletion, indicates the involvement of Ca2+-induced thiol protease in the observed degradation of membrane proteins. The results ind icate that an altered Ca2+ homeostasis in erythrocytes following leishmania l infection causes enhanced cellular accumulation of Ca2+, which in turn ma y lead to haemolysis in experimental visceral leishmaniasis.