Uso de parasitas transgÃnicos para caracterizar o papel funcional de genes envolvidos na resistÃncia a lise pelo complemento em Tripanosomatideos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

Tripanosoma cruzi and Leishmania are obligated intracellular parasites in cells of hosts mammals. However the parasites can be found in three different habitats during its cycle of life: the intestine of the insect vector, the extracellular space of the vertebrate host and in cells of the fagocÃtico system. After inoculation of metaciclic tripomastigotas forms and promastigotas forms of T. cruzi and Leishmania respectively, the parasites are displayed to the potential lÃtics effect of the normal serum and lyses mediated by the complement can compromise the survival of the parasite. The infection human being mediated for parasites is a process extremely fast and the parasites must make use of strategies of evasion of lyse immediately after the inoculation to escape of the deleterious effect of the serum after activation of the system complement. Distinct molecules of the cellular surface in different organisms are involved in the resistance processes lyse for the complement. In Trypanosoma cruzi was identified a molecule involved with the resistance lyse for the complement. A protein of 160 kDa called CRP (complement regulatory protein) of T. cruzi restricts the activation of the classic and alternative pathways preventing the proteolÃtics action of the C3 convertase. In Leishmania molecules such as gp-63, LPG seem to be responsible for the evasion of lyse, but the mechanisms still are not clear. One another example of resistance mechanism lyse for the complement is conferred by a protein of 32 kDa called CRIT (C2 receptor inhibitor trispaning) express in the surface adult forms of Schistossoma that if binds to the C2 component preventing the formation of the C3 convertase. The goal of this work is to understand the activation of the complement system for parasites and to identify molecules involved with lyse for the complement in tripanosamatideos. Through procedures of transfecÃÃo and overexpresion of CRP and CRIT in T. cruzi and Leishmania we analyze the function of these genes in transgenics and wild parasites. For this purpose we have made differents constructions with CRP and CRIT genes using these vectors. They had been carried through kinetic of activation of the complement in different tripanosomatideos with the use of normal human serum to evaluate the effect of the complement on the parasites. The acquisition of resistance to lyse mediated by the complement with the use of different transgenics parasites favored the understanding of the mechanisms that determine the infection and opens possibilities of development of chemotherapeutics measures for control of the illnesses

ASSUNTO(S)

genes genetica parasitas transgÃnicos tripanosomatideos resistÃncia a lise

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