Abstract
Trypanosoma cruzi proteinases are very likely involved in host-cell invasion. Physiological plasma-proteinase inhibitors from the macroglobulin (MG) family, among them alpha-2-macroglobulin (A2M), are found in tissues and in the plasma of mammals. By complexing to all classes of proteinases, MGs inhibit their action on high-molecular-weight substrates. In vitro studies have shown that A2M impairsT. cruzi proteases and, consequently, the parasite's ability to invade host cells and enhances the phagocytic and microbicidal actions of resident macrophages againstT. cruzi. To test the hypothesis of a putative “protective” effect for MG, we quantified it in BALB/cj mice during the course of an experimentalT. cruzi infection, comparing a posteriori the levels in mice that died with those in animals that survived, which were considered as being susceptible and resistant to the infection, respectively. The results showed that surviving mice showed an increase in plasma concentrations of MG during the first few weeks after the infection, whereas the levels in mice that died during the acute phase did not differ significantly from those in non-infected mice. These findings and the previous in vitro data indicate a role for physiological proteinase inhibitors, particularly alpha-macroglobulins, in resistance toT. cruzi infection, whereby a balance between parasite proteases and host protease inhibitors may be crucial. MG may thus participate in the complex network of reactions involved in the early acute phase of the disease and contribute by confering to the host an ability to survive the infection.
Similar content being viewed by others
References
Abe K, Yamamoto K, Sinohara H (1989) Proteinase inhibitory spectrum of mouse murinoglobulin and alpha-macroglobulin. J Biochem 106:564–568
Andrade V, Barral-Neto M, Andrade SG (1985) Patterns of resistance of inbred mice toTrypanosoma cruzi are determined by the parasite strain. Braz J Med Biol Res 18:499–506
Araujo-Jorge TC, De Souza W (1984) Effect of carbohydrates, periodate and enzymes in the process of endocytosis ofTrypanosoma cruzi by macrophages. Acta Trop (Basel) 41:17–28
Araujo-Jorge TC, Sampaio EP, De Souza W (1986)Trypanosoma cruzi: inhibition of host cell uptake of infective bloodstream forms by alpha-2-macroglobulin. Z Parasitenkd 72:323–329
Araujo-Jorge TC, Meirelles MNL, Isaac L (1990)Trypanosoma cruzi: killing and enhanced uptake by resident peritoneal macrophages treated with alpha-2-macroglobulin. Parasitol Res 76:545–552
Brener Z (1962) Therapeutic activity and criterion of cure on mice experimentally infected withTrypanosoma cruzi. Rev Inst Med Trop Sao Paulo 4:389–398
Cardoni RL, Tottenberg ME, Segura EL (1990) Increased production of reactive oxygen species by cells from mice acutely infected withTrypanosoma cruzi. Cell Immunol 128:11–21
Carlier Y, Bout D, Fruchart JC, Desreumaux C, Dewailly P, Sezille A, Jaillard J (1978) Inhibition enzyme-immunoassay. Application to human apolipoprotein B. J Immunol Methods 21:317–324
Carlier Y, Bout D, Capron A (1981) Enzymo-immunoassays. Bull Inst Pasteur (Paris) 79:313–382
Carlier Y, Rivera MT, Truyens C, Goldman M, Lambert P, Flament J, Vray B (1987) Pregnancy and humoral immune response in mice chronically infected byTrypanosoma cruzi. Infect Immun 55:2496–2501
Hanson WL, Roberson EL (1974) Density of parasites in various organs and the relation to numbers of trypomastigotes in the blood during acute infections ofTrypanosoma cruzi in mice. J Protozool 21:512–517
Hauschka TS (1947) Sex of host as a factor in Chagas' disease. J Parasitol 33:399–404
Isaac L, Pereira M, Santos M, Sampaio EP, Lima NR, Lage MF, Araujo-Jorg TC (1990)Trypanosoma cruzi: plasma levels of alpha-2-macroglobulin during experimental murine infections with reticulotropic and myotropic strains. Parasitol Res 76:726–728
James K (1990) Interactions between cytokines and alpha-2-macroglobulin. Immunol Today 11:163–166
Koj A (1984) Definition and classification of acute-phase proteins. In: Lypte G (ed) The acute phase response to injury and infection, ch 12 Elsevier, Amsterdam, pp 139–144
Koj A, Magielska-Zero D, Kurdowska A, Bereta J (1988) Proteinase inhibitors as acute phase reactants: regulation of synthesis and turnover. In: Horl WH, Heidland A (eds) Proteases II: potential role in health and disease. Plenum, New York, pp 171–181
Nogueira N, Gordon S, Cohn Z (1977)Trypanosoma cruzi: the immunological induction of plasminogen activator requires thymus-derived lymphocytes. J Exp Med 146:172–183
Ouaissi MA, Cornette J, Capron A (1985)Trypanosoma cruzi: modulation of parasite-cell interaction by plasma fibronectin Eur J Immunol 15:1096–1101
Overbergh L, Torrekens S, Van Leuven F, Van den Berghe H (1991) Molecular characterization of the murinoglobulins. J Biol Chem 266:16903–16910
Piras MM, Henriquez D, Piras R (1985) The effect of proteolytic enzymes and protease inhibitors on the interaction ofTrypanosoma cruzi-fibroblasts. Mol Biochem Parasitol 14:151–163
Russo M, Starobinas N (1990) Macrophage activation and resistance toTrypanosoma cruzi infection. Res Immunol 142:144–146
Scharfstein J, Barcinski MA, Leon L (1982) Induction of acutephase protein serum amyloid P in experimental Chagas' disease. Infect Immun 35:46–51
Sottrup-Jensen L (1989) Alpha-macroglobulins: structure, shape, and mechanism of proteinase complex formation. J Biol Chem 254:11539–11542
Trischman TM (1988) Natural and acquired resistance toTrypanosoma cruzi. In: Eisenstein TK, Actor P, Friedman H (eds) Host defenses to intracellular pathogens. Plenum, New York, pp 365–382
Van Leuven F (1984) Human alpha-2-macroglobulin: primary amines and molecular mechanism of endoprotease inhibition and receptor-mediated endocytosis. Mol Cell Biochem 58:121–128
Van Leuven F, Marynen P, Cassiman J-J, Van den Bergue H (1987) A mouse monoclonal antibody to human alpha-2-macroglobulin (A2M) cross-reacts with A2M from mouse epitope mapping and characterization of the subunit structure of murine A2M. J Biochem 101:1181–1189
Author information
Authors and Affiliations
Additional information
This study was financially supported by CNPq, FIOCRUZ, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, FAPERJ, ULB/FNRS, KUL/ FGWO, Gedocertivorde Acties, USAP, and by a post-doctoral fellowship (awarded to T.C.A.-J.) sponsored by CNPq in Belgium.
Rights and permissions
About this article
Cite this article
Araujo-Jorge, T.C., Lage, MJ.F., Rivera, M.T. et al. Trypanosoma cruzi: Enhanced alpha-macroglobulin levels correlate with the resistance of BALB/cj mice to acute infection. Parasitol Res 78, 215–221 (1992). https://doi.org/10.1007/BF00931729
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00931729