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Browsing by Subject "C4bp"

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  • Holopainen, Saila (University of HelsinkiHelsingin yliopistoHelsingfors universitet, 2008)
    Malaria remains one of the major health problems in many tropical countries, especially in sub-Saharan Africa. Among the most characteristic features of the malaria pathogens, protozoan parasites of the genus Plasmodium, is their ability to evade the immune defences of the host for extended periods of time. The complement system (C) is an essential part of the innate system in the first line of defense. It consists of over 30 soluble or membrane-bound components. C can be activated through three different (the classical, the lectin and the alternative) pathways, and the activation is tightly regulated. All three pathways converge at the C3 level and activation continues through the terminal pathway. C functions include lysis of microbes, opsonization, attraction and activation of leucocytes and enhancement of the inflammatory response. In the present study the aim was to look into whether Plasmodium falciparum (Pf) interferes with the complement at the level of C3 by accelerating C3b inactivation and thus inhibit the amplification of the C cascade. Considering the characteristics of Pf infection it is obvious that the plasmodia must somehow avoid complement attack. Flow cytometric analysis (FACS), enzyme-linked immunosorbent assays (ELISA), immunoblotting assays and matrix assisted laser desorption/ionization (MALDI) were used to determine if Pf evade C attack by acquisition of the host C inhibitors, factor H (FH) and C4b binding protein (C4bp), from serum. FH is the major regulator of the alternative-pathway while C4bp is an inhibitor of the classical-pathway. We also studied binding of complement components, especially C3, to Pf cells. In our studies, there appeared to be an elevated binding of FH to Pf parasitized erythrocytes in FACS. In immunoblotting assays, a putative C3-binding merozoite-stage Pf protein was observed. Previously, it has been suggested that Plasmodium spp. merozoites adsorb C3 fragments to their surface to gain entry into erythrocytes via CR1-receptor. No binding of C4bp was detected. Further studies are required to reveal the complement resistance mechanisms of Pf. Elucidation of Pf-C interactions will be of great importance for our understanding of the principles of Plasmodium immunoevasion that affect directly the virulence of the microbe. By identifying factors whereby Pf evades C, it is possible to understand better how the microbe causes disease and, ultimately, how this could be prevented.