Hostname: page-component-848d4c4894-nr4z6 Total loading time: 0 Render date: 2024-06-09T18:14:31.291Z Has data issue: false hasContentIssue false
  • English
  • Français

Schistosoma mansoni host–parasite relationship: interaction of contrapsin with adult worms

Published online by Cambridge University Press:  06 April 2009

J. Modha  and
M. J. Doenhoff
J. Modha
Affiliation:
Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ
M. J. Doenhoff
Affiliation:
School of Biological Sciences, University College of North Wales, Bangor, Gwynedd LL57 2UW
Get access Rights & Permissions [Opens in a new window]

Summary

Contrapsin, a serine protease inhibitor (serpin) present in mouse serum, was compared with that found in adult Schistosoma mansoni worm homogenates, which although immunologically identical to contrapsin in mouse serum, had a higher molecular weight in Western blotting. Immunolocalization studies demonstrated parasite-associated contrapsin on the surface and interstitial cells of adult male worms. After extraction of these parasites with Triton X-114, contrapsin was found in the aqueous phase of the detergent, suggesting it is unlikely to be an integral membrane protein. Treatment of adult worms with deoxycholate resulted in a change in the electrophoretic behaviour of worm-derived contrapsin. Parallel studies with trypsin suggested this was due to interaction of the serpin with a protease. Using porcine pancreatic trypsin as a model for a putative schistosome protease reacting with contrapsin, we have shown that trypsin, following complex formation with contrapsin, loses immunogenicity. Thus, when contrapsin–trypsin complexes were used as immunogen, the resulting antisera contained antibodies to contrapsin and contrapsin–trypsin complexes only, and none to native trypsin. Thus, epitopes characterizing native trypsin were presumably either masked following complex formation with contrapsin, or their processing and presentation to antigen presenting cells was suppressed, so that an antibody response was not mounted against them. These observations encourage speculation that S. mansoni may be elaborating an immune evasion strategy whereby immunologically sensitive proteases are first complexed with host serpins, which would render them immunogenically inert, and then cleared from the circulation by the host's reticulo-endothelial system. In this way the immune system would be unable to ‘see’ sensitive parasite proteases sufficiently to mount a response against the parasite.

Keywords

Schistosoma mansoniserine protease inhibitor (serpin)contrapsintrypsinserpin–enzyme complexesdeoxycholateTriton X-114
Type
Research Article
Information
Parasitology , Volume 109 , Issue 4 , November 1994 , pp. 487 - 495
Copyright
Copyright © Cambridge University Press 1994

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Amiri, P., Locksley, R. M., Parsow, T. G., Sadick, M., Rector, E., Ritter, D. & McKerrow, J. H. (1992). Tumour necrosis factor restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature, London 356, 604–7.CrossRefGoogle ScholarPubMed
Baumstark, J. S. (1967). Studies on the elastase–serum protein interaction. 1. Molecular identity of the inhibitors in human serum and direct demonstration of the inhibitor–elastase complexes by zone and immunoelectrophoresis. Archives of Biochemistry and Biophysics 118, 619–30.Google Scholar
Bordier, C. (1981). Phase separation of integral membrane proteins in Triton X-114. Journal of Biological Chemistry 256, 1604–7.Google Scholar
Bradford, M. M. (1976). A rapid method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–54.Google Scholar
Clegg, J. A., Smithers, S. R. & Terry, R. J. (1971). Acquisition of human antigens by S. mansoni during cultivation in vitro. Nature, London 232, 653–4.CrossRefGoogle Scholar
Colley, D. G. & Nix, N. A. (1992). Do schistosomes exploit the host pro-inflammatory cytokine TNFα for their own survival? Parasitology Today 11, 355–7.Google Scholar
Damian, R. T., Greene, N. D. & Hubbard, W. J. (1973). Occurrence of mouse alpha-2-macroglobulin antigenic determinants on Schistosoma mansoni adults, with evidence on their nature. Journal of Parasitology 59, 67–73.Google Scholar
Doenhoff, M. J., Hassounah, O. A. & Lucas, S. B. (1985). Does the immunpathology induced by schistosome eggs potentiate parasite survival? Immunology Today 6, 203–6.Google Scholar
Doenhoff, M. J., Musallam, R., Bain, J. & McGregor, A. (1978). Studies on the host–parasite relationship on S. mansoni-infected mice: the immunological dependence of parasite egg excretion. Immunology 35, 771–8.Google Scholar
Dresden, M. H. (1982). Proteolytic enzymes of Schistosoma mansoni. Acta Leidensia 49, 81–99.Google Scholar
Dunne, D. W., Agnew, A. M., Modha, J. & Doenhoff, M. J. (1986). Schistosoma mansoni egg antigens: preparation of rabbit antisera with monospecific immunoprecipitating activity, and their use in antigen characterization. Parasite Immunology 8, 575–86.Google Scholar
Harrison, R. & Doenhoff, M. J. (1983). Retarded development of Schistosoma mansoni in immunosuppressed mice. Parasitology 86, 429–38.Google Scholar
Helenius, A. & Simons, K. (1975). Solubilization of membranes by detergents. Biochimica et Biophysica Acta 415, 29–79.CrossRefGoogle ScholarPubMed
Hill, R. E., Shaw, P. H., Boyd, P. A., Baumann, H. & Hastie, N. D. (1984). Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions. Nature, London 311, 175–7.Google Scholar
Kemp, W. M., Damian, R. T., Green, N. D. & Lushbaugh, W. B. (1976). Immunocytochemical localization of mouse alpha-2-macroglobulin-like antigenic determinants on Schistosoma mansoni adults. Journal of Parasitology 62, 413–19.CrossRefGoogle Scholar
Laemmli, U. K. (1970). Cleavage of structural proteins during assembly of bacteriophage T4. Nature, London 227, 680–5.Google Scholar
Mast, A. E., Enghild, J. J., Pizzo, S. V. & Salvesen, G. (1991). Analysis of the plasma elimination kinetics and conformational stabilities of native, proteinase-complexed, and reactive-site cleaved serpins: comparison of α1-antichymotrypsin, antithrombin III, α1-antiplasmin, angiotensinogen and ovalbumin. Biochemistry 30, 1723–30.Google Scholar
McKerrow, J. H. (1987). Workshop summary: The role of proteases in the pathogenesis and immune response to parasitic disease. In Molecular Strategies of Parasitic Invasion (ed. Agabian, N., Goodman, H. & Nogueira, N.), pp. 553–57. London: Alan R. Liss.Google Scholar
McKerrow, J. H. & Doenhoff, M. J. (1988). Schistosome proteases. Parasitology Today 4, 334–40.CrossRefGoogle ScholarPubMed
McKerrow, J. H., Pino-Heiss, S., Lindquist, R. & Werb, Z. (1985). Purification and characterization of an elastinolytic proteinase secreted by cercariae of Schistosoma mansoni. Journal of Biological Chemistry 260, 3703–7.CrossRefGoogle ScholarPubMed
McLaren, D. J. & Terry, R. J. (1982). The protective role of acquired host antigens during schistosome infection. Parasite Immunology 4, 129–48.Google Scholar
Modha, J., Parikh, V., Gauldie, J. & Doenhoff, M. J. (1988). An association between schistosomes and contrapsin, a mouse serine protease inhibitor (serpin). Parasitology 96, 99–109.Google Scholar
Nathoo, S., Rasums, A., Katz, J., Ferguson, W. S. & Finlay, T. H. (1982). Purification and properties of two different α1-protease inhibitors from mouse plasma. Archives of Biochemistry and Biophysics 219, 306–15.CrossRefGoogle Scholar
Neugebauer, J. (1990). A Guide to the Properties and Uses of Detergents in Biology and Biochemistry. Calbiochem Biochemicals booklet: Calbiochem Corporation (La Jolla, California).Google Scholar
Ouchterlony, O. (1958). Diffusion in gel methods for immunological analysis. Progress in Allergy 5, 1–78.Google Scholar
Perlmutter, D. H., Glover, G. I., Rivetna, M., Schasteen, C. S. & Fallon, R. J. (1990 a). Identification of a serpinenzyme complex receptor on human hepatoma cells and human monocytes. Proceedings of the National Academy of Sciences, USA 87, 3753–7.Google Scholar
Perlmutter, D. H., Joslin, G., Nelson, P., Schasteen, C., Adams, S. P. & Fallon, R. J. (1990 b). Endocytosis and degradation of α1-antitrypsin-protease complexes is mediated by the serpin-enzyme complex (SEC) receptor. Journal of Biological Chemistry 265, 16713–16.Google Scholar
Pryde, J. G. (1986). Triton X-114: a detergent that has come in from the cold. Trends in Biochemical Sciences 11, 160–3.Google Scholar
Smithers, S. R. & Terry, R. J. (1965). The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitology 55, 695–700.Google Scholar
Smithers, S. R., Terry, R. J. & Hockley, D. J. (1969). Host antigens in schistosomiasis. Proceedings of the Royal Society of London, B171, 483–94.Google ScholarPubMed
Takahara, H. & Sinohara, H. (1982). Mouse plasma trypsin inhibitors: Isolation and characterization of α1-antitrypsin and contrapsin, a novel trypsin inhibitor. Journal of Biological Chemistry 257, 2438–46.Google Scholar
Takahara, H. & Sinohara, H. (1983). Inhibitory spectrum of mouse contrapsin and α1-antitrypsin against mouse serine proteases. Journal of Biochemistry 93, 1411–19.Google Scholar
Towbin, H., Staehelin, T. & Gordon, J. (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proceedings of the National Academy of Sciences, USA 76, 4350–4.Google Scholar
Toy, L., Petitt, M., Wang, Y. F., Hedstrom, R. & McKerrow, J. H. (1987). Molecular Paradigms for Eradicating Helminthic Parasites. London: Alan R. Liss.Google Scholar
Travis, J. & Salvesen, G. S. (1983). Human plasma proteinase inhibitors. Annual Reviews in Biochemistry 52, 655–709.Google Scholar
Watts, C. & Lanzavecchia, A. (1993). Suppressive effect of antibody on processing of T cell epitopes. Journal of Experimental Medicine 178, 1459–63.Google Scholar
Wieme, R. J. (1959). An approved technique for agar-gel electrophoresis on agar-gel microscopic slides. Clinica Chimica Acta 4, 317–21.Google Scholar