Abstract
Alpha-Macroglobulins (AM) are protease inhibitors with important roles in inflammation and in immunomodulation that behave as acute-phase proteins in many experimental models. In the present work the levels of AM in the plasma of outbred Swiss albino mice acutely infected withTrypanosoma cruzi were studied. The results showed that increased levels of AM were present in the majority of the infected mice and that AM levels increased independently of the rise in parasitaemia. There was a high degree of heterogeneity in the intensity of the modulation of AM levels as well as in the kinetics of AM synthesis. This heterogeneity was related neither with the intensity of infection nor with the sex of the host. No correlation between AM levels and survival to the acute phase could be observed in the outbred mice. The consequence of such a heterogeneity is unclear, although AM as immunoregulatory molecules could play a role in the development of the symptoms of the chronic phase of Chagas' disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akira S, Kishimoto T (1992) IL-6 and NF-IL6 in acute-phase response and viral infections Immunol Rev 127:25–50
Araújo-Jorge TC, Meirelles MNL, Isac L (1986)T. cruzi: inhibition of host cell uptake of infective bloodstream forms by alpha-2-macroglobulin. Z Parasitenkd 72:323–329
Araújo-Jorge TC, Laje MJF, Rivera MT, Carlier Y, Van Leuven F (1992)T. cruzi: enhanced alpha-macroglobulin levels correlate with the resistance of Balb/cj mice to acute infection. Parasitol Res 78:215–221
Brener Z (1992) Immune response and immunopathology inT. cruzi infection. In: Wendel W, Brener Z, Camargo ME, Rassi A (eds) Chagas disease (American trypanosomiasis): its impact on transfusion and clinical medicine. International Society of Blood Transfusion, Sociedade Brasileira de Hematologia, São Paulo, pp 31–47
Chu CT, Pizzo SV (1993) Receptor mediated antigen delivery into macrophages. Complexing antigen to alpha-2-macroglobulin enhances presentation to T cells. J Immunol 150:48–58
Chu CT, Oury TD, Enghild JJ, Pizzo SV (1994) Adjuvant-free in vitro targeting: antigen delivery byα 2-macroglobulin enhances antibody formation. J Immunol 152:1538–1545
Gazinelli RT (1991) Natural anti-gal antibodies prevent rather than cause autoimmunity in human Chagas' disease. Res Immunol 142:164–167
Hanson WL, Roberson EL (1974) Density of parasites in various organs and the relation to numbers of trypomastigotes in the blood during acute infections ofT. cruzi in mice. J Protozool 21:512–517
Hoffman MR, Pizzo SV, Weinberg JB (1987) Modulation of mouse peritoneal macrophage Ia and human peritoneal macrophage HLA-DR expression byα 2-macroglobulin “fast” forms. J Immunol 139:1885–1890
Isaac I, Pereira M, Santos M, Sampaio EP, Lima NR, Lage MJF, Araújo-Jorge TC (1990)T. cruzi plasma levels of alpha-2-macroglobulin during experimental murine infections with reticulotropic and myotropic strains. Parasitol Res 76:726–728
Koj A (1985) Definition and classification of acute phase proteins. In: Gordon AH, Koi A (eds) The acute phase response to injury and infection. Elsevier, Amsterdam New York Oxford 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 roles in health and disease. Plenum, New York, pp 171–181
Luz MRMP, Van Leuven F, Araújo-Jorge TC (1994a) An inhibition ELISA for the detection of alpha-macroglobulins in mouse plasma. Mem Inst Oswaldo Cruz 89:203–207
Luz MRMP, Van Leuven F, Araújo-Jorge TC (1994b) Heterogeneity in the synthesis of acute-phase proteins among mice from different inbred strains infected withTrypanosoma cruz. Parasitol Res 80:439–441
Medrano-Mercado N, Luz MRMP, Cabello PH, Tapia GT, Van Leuven F, Araújo-Jorge TC (1994) Acute Chagas' disease: plasma levels of alpha-2-macroglobulin and C-reactive protein in children under 13 years in a highly endemic area of Bolivia. J Trop Pediatr 89:203–207
Nabors GS, Tarleton RL (1991) Differential control of interferon-γ and IL-2 production duringT. cruzi infection. J Immunol 146: 3591–3598
Osada T, Noro N, Kuroda Y (1987) Murine T cell proliferation can be specifically augmented by macrophages fed with specific antigens:α 2-macroglobulin conjugate. Biochem Biophys Res Commun 146:23–28
Osada T, Noro N, Kuroda Y (1988) Antibodies against viral proteins can be produced effectively in response to the increased uptake of alpha-2-macroglobulin viral protein conjugate by macrophages. Biochem Biophys Res Commun 150: 883–886
Petray PB, Rottenberg ME, Bertot G, Corral RS, Diaz A, Orn A, Grinsten S (1993) Effect of anti-γ-interferon anti-interleukin-4 administration on the resistance of mice against infection with reticulotropic and myotropic strains ofTrypanosoma cruzi. Immunol Lett 35:77–80
Ribeiro dos Santos R, Rossi MA, Lans JL, Silva JS, Savino W, Mengel J (1992) Anti-C4 abrogates rejection and reestablishes long-term tolerance to syngeneic newborn hearts grafted in mice chronically infected withT. cruzi. J Exp Med 175:29–39
Scharfstein J, Barcinski MA, Leon LL (1982) Induction of ocutephase protein serum amyloid P in experimental Chagas' disease. Inf/Immun 35:46–51
Tarleton RL (1990) Depletion of CD8+ T cells increases susceptibility and reverses vaccine/induced immunity in mice infected withT. cruzi. J Immunol 144:717–724
Tarleton RL (1991) Regulation of immunity inT. cruzi infection. Exp Parasitol 73:106–109
Torrico F, Heremans H, Rivera MT, Van Marck E, Billian A, Carlier Y (1991) Endogenous interferon-γ is required for resistance toT. cruzi infection in mice. J Immunol 146:3626–3662
Van Leuven F (1982) Humanα 2-macroglobulin: structure and function. Trends Biochem Sci 7:185–187
Van Leuven F, Marynen P, Cassiman JJ, Vandenberg HE (1987) A mouse monoclonal antibody to human alpha-2-macroglobulin (α 2M) crossreacts withα 2M from mouse: epitope mapping and characterization of subunit structure of murineα 2M. J Immunol 101:1181–1189
Van Leuven F (1982) Humanα 2-macroglobulin: structure and function. Trends Biochem Sci 7:185–187
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Luz, M.R.M.P., van Leuven, F. & de Araújo-Jorge, T.C. Heterogeneity in the synthesis of alpha-macroglobulins in outbred Swiss albino mice acutely infected withTrypanosoma cruzi . Parasitol Res 81, 662–667 (1995). https://doi.org/10.1007/BF00931843
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00931843