Trypanosoma cruzi: Inhibition of host cell uptake of infective bloodstream forms by alpha-2-macroglobulin

Tc, de Araújo-Jorge; Ep, Sampaio; W, de Souza

doi:10.1007/bf00928742

Cited by 15 publications

(5 citation statements)

References 16 publications

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“…Cysteine proteinases are more active at low pH (Bontempi et al 1989), thus explaining the increased binding of N-A2M to T. cruzi observed at acidic pH. The present results showing N-A2M binding to the T. cruzi surface agree with our previous work showing that pretreatment of parasites with N-A2M inhibited their invasion into host cells (Araú jo-Jorge et al 1986), probably by impairing parasite proteases necessary for processing of trypomastigote surface ligands involved in the adhesion and interiorization steps of the infection. In the case of the interaction of human A2M with Leishmania promastigote surface protease, the reaction could be detected with the purified protease but not using intact parasites (Heumann et al 1989).…”

Section: Discussionsupporting

confidence: 82%

“…In the past decade, indirect evidence has suggested that proteases located on the surface of trypomastigotes could render them infective for host cells (Piras et al 1985;Araú jo-Jorge et al 1986). Since then, other authors have shown that some proteases are involved ''in vitro'' in processes of host-cell invasion (Souto-Padró n et al 1990;Meirelles et al 1992) and intracellular differentiation (Bonaldo et al 1991a, b).…”

Section: Discussionmentioning

confidence: 99%

“…The parasite infects and proliferates ''in vitro'' and ''in vivo'' in a variety of vertebrate cells, including resident nonactivated macrophages. Surface components of the parasite and of the host cells have been implicated in the processes of cell recognition and cell-cell interaction, and there are findings suggesting the involvement of parasite proteinases in T. cruzi invasion (Araú jo- Jorge et al 1986;Souto-Padró n et al 1990;Meirelles et al 1992).…”

Section: Introductionmentioning

confidence: 99%

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Alpha-2-macroglobulin binds to the surface of Trypanosoma cruzi

Coutinho

Cavalcanti

Leuven

et al. 1997

Parasitology Research

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Trypanosoma cruzi, the causative agent of Chagas disease, infects vertebrate cells after an initial step of parasite/host-cell recognition. Alpha-2-macroglobulin (A2M), an important type of physiological proteinase inhibitor found in tissues and in the plasma of mammals, inhibits cell invasion by T. cruzi and accumulates in sites of the inflamed myocardium associated with parasite antigens. To study whether A2M would bind to T. cruzi, an indirect immunofluorescence reaction was performed using two different anti-mouse A2M sera. Intense labeling was observed in the membrane lining the cell body and the flagellum of bloodstream trypomastigotes obtained from experimentally infected mice in the peak of parasitemia, suggesting that the antisera recognize plasma A2M associated with the parasite surface. Metacyclic trypomastigotes obtained in a serum-free defined medium reacted with anti-A2M only after previous incubation with purified human A2M. Enzyme-linked immunosorbent assay (ELISA) studies were applied to characterize better the binding of native (N-A2M) and of proteinase-complexed (P-A2M) forms of A2M. The "in vitro" binding of N-A2M to trypomastigotes was better at pH 5.0, followed by pH 10.0 and pH 7.4. Cysteinly and serine proteinase inhibitors, E-64 and STI, respectively, inhibited the reaction. P-A2M also bound to T. cruzi in a dose-dependent way. Flow-cytometry studies showed that about 80% of the parasites stained with fluorescein isothiocyanate (FITC)-labeled P-A2M (50 micrograms/ml) with high affinity at pH 7.4 (but also at pH 10.0) in a process that was reverted by the addition of unlabeled P-A2M or the calcium-chelator agent EDTA and also by incubation at an acid pH (4.0). These results suggest that (a) native-A2M binds to T. cruzi proteinase(s) and (b) T. cruzi expresses a receptor(s) that binds proteinase-complexed A2M.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alpha-2-macroglobulin binds to the surface of Trypanosoma cruzi

Coutinho

Cavalcanti

Leuven

et al. 1997

Parasitology Research

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“…We supposed that the lower tissue T. cruzi parasitism found in infected C3H/HeJ male mouse could denote an inhibitory effect of A2M since in vitro studies revealed that the addition of A2M to the interaction medium impaired the parasite invasion (Araújo-Jorge et al, 1986). In fact, analysis of T. cruzi infection in these experimental models must take into account the differences in the steady state of AM and A2MR/LRP between the uninfected male mice that we presently reported.…”

Section: Discussionmentioning

confidence: 80%

Differential Expression of mRNA Coding for the Alpha-2-macroglobulin Family and the LRP Receptor System in C57BL/6J and C3H/HeJ Male Mice.

Soeiro

Paiva

Waghabi

et al. 2001

Cell Struct. Funct.

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ABSTRACT. Expression of mouse A2M (MAM), murinoglobulin (MUG), the A2M receptor or LDL-Receptor related protein (A2MR/LRP) and the Receptor Associated Protein (RAP) were measured by northern blotting of mRNA isolated from liver, heart and peritoneal macrophages from C3H/HeJ and C57BL/6J (B6) mice. Marked differences between males of the two mouse strains were observed for MAM and MUG mRNA levels in liver, which were reflected in plasma levels of both proteinase inhibitors, as confirmed by immune-electrophoresis. C3H/HeJ mice had higher levels of the MAM and MUG mRNA and their corresponding plasma proteins than B6 mice. B6 mice expressed higher levels of LRP mRNA relative to C3H/HeJ mice but had lower levels of RAP mRNA. LRP receptor activity, assayed by fluoresceinated-A2M binding, was higher in B6 cells. The present data contribute to the knowledge of genetic background characteristics among male mouse of these two strains, which can take part in many biological events such as lipid metabolism, inflammation and immune response to different infectious agents.

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“…Ultrastructural studies in T. cruzi have been conducted in order to define the localization and distribution of peptidases in the parasite since the involvement of peptidases in the process of T. cruzi-host cell interaction was described [105,106]. Further studies not only confirmed those findings but also showed the role of peptidases in the intracellular survival, replication and differentiation of the parasite and in disease pathology [23,32,58,90,107,108].…”

Section: Ultrastructural Studiesmentioning

confidence: 99%

Trypanosoma cruzi Peptidases: An Overview

Vermelho¹,

Melo²,

Soares³

et al. 2010

TOPARAJ

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Peptidases are a group of enzymes which have a catalytic function that is to hydrolyze peptide bonds of proteins. The enzymes that hydrolyze peptide bonds at the amino-or carboxy-terminus are classified as exopeptidases, and those that cleave peptide bonds inside the polypeptide are endopeptidases. Endopeptidases, such as cysteine-, metalo-, serine-and threonine peptidases as well as some exopeptidases, have been characterized in Trypanosoma cruzi. Understanding the pathogenesis of T. cruzi requires the identification of functional properties of those peptidases, as they are implied in virulence, are important for host-parasite interactions and are critical for successful survival in their hosts. Here we examine the main T. cruzi peptidases, focusing on their biological roles, especially concerning the parasite-mammalian host relations.

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Trypanosoma cruzi: Inhibition of host cell uptake of infective bloodstream forms by alpha-2-macroglobulin

Cited by 15 publications

References 16 publications

Alpha-2-macroglobulin binds to the surface of Trypanosoma cruzi

Alpha-2-macroglobulin binds to the surface of Trypanosoma cruzi

Differential Expression of mRNA Coding for the Alpha-2-macroglobulin Family and the LRP Receptor System in C57BL/6J and C3H/HeJ Male Mice.

Trypanosoma cruzi Peptidases: An Overview

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