Trypanosoma cruzi causes Chagas' disease, an incurable illness affecting more than 2 million people in Latin America. The mechanism underlying the molecular basis of T. cruzi-host interaction is just beginning to be understood. One of these mechanisms could very well be mediated to a novel class of trypanosome proteins, that were discovered because of their specific reaction with the proteoglycan heparin. The heparin-binding proteins can be readily isolated in five fractions by affinity chromatography on heparin coupled to Sepharose. Two of the five fractions are potent inhibitors of infection, and both are capable of agglutinating human and rabbit, erythrocytes in a sialic acid dependent manner. The active fractions exhibit only four major bands in autoradiographs and thus are already highly purified. The heparin-binding proteins are developmentally regulated for they are detectable only in trypomastigotes, the infective stage of T. cruzi. To gain further insights into the mechanism governing the role in T.cruzi-host cell interaction that may be played by the heparin-binding proteins (i.e., the hemagglutinins and/or the factor active in inhibiting infection), it is proposed to determine whether the abundance of active materials is correlated with the biological properties of clones and strains of T. cruzi, to isolate the active procedures of biochemistry and cell biology, to study the interaction of the active materials with host cells at the molecular level using biochemical and immunological tools, and to clone and characterize the gene of relevant materials to learn more about structure-function relationship of the heparin-binding proteins. The results of the proposed experiments could lead to be development of reagents useful for ligand- and immunotherapy of Chagas' disease, and could further our understanding of T. cruzi-host interaction at the molecular level.
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