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The purification, characterization, serological activity and hepatotoxic properties of two cationic glycoproteins (α1 and ω1) from Schistosoma mansoni eggs

Published online by Cambridge University Press:  06 April 2009

D. W. Dunne
Affiliation:
Division of Microbiology and Parasitology, Department of Pathology, Cambridge University, Cambridge CB2 1QP
F. M. Jones
Affiliation:
Division of Microbiology and Parasitology, Department of Pathology, Cambridge University, Cambridge CB2 1QP
M. J. Doenhoff
Affiliation:
School of Biological Sciences, University College of North Wales, Bangor, Gwynedd LL57 2UW

Abstract

T cell-deprived mice acutely infected with S. mansoni suffer microvesicular hepatocyte damage which is not seen in infected, immunological intact animals. A cationic fraction (CEF6) of the PBS-soluble portion of S. mansoni eggs (SEA) induces antibodies which, on passive transfer, prevent hepatocyte damage. CEF6 contains 2 antigens, ω1 and α1, and has also been shown to be a useful serodiagnostic reagent. This paper describes the purification and characterization of the 2 antigens present in CEF6. ω1 is a monomeric glycoprotein with a pI > 9·0 and a molecular weight of 31 kDa. α1 consists of two immunologically cross-reactive dimers, 41 and 36 kDa in non-reducing conditions, each of which consists of one unique and one common glycoprotein subcomponent. In ELISA with mouse and human infection sera ω1 is shown to be S. mansoni specific and is better able to distinguish S. mansoni infections from other schistosome infections than are unfractionated SEA, CEF6 or α1. Passive transfer of monospecific anti-ω1 sera into S. mansoni infected, T cell-deprived mice completely prevented the occurrence of microvesicular hepatocyte damage in these animals. Monospecific anti-α1 serum had no hepatoprotective capacity.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1991

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References

Agnew, A. M., Murare, H. M., Lucas, S. B. & Doenhoff, M. J. (1989). Schistosoma bovis as an immunological analogue of S. haematobium. Parasite Immunology 11, 329–40.CrossRefGoogle ScholarPubMed
Bloch, E. H., Abdel-Wahab, M. F. & Warren, K. S. (1972). In vitro microscopic observation of the pathogenesis and pathophysiology of hepatosplenic schistosomiasis in the mouse liver. American Journal of Tropical Medicine and Hygiene 21, 546–57.CrossRefGoogle Scholar
Buchanan, R. D., Fine, D. P. & Colley, D. G. (1973). Schistosoma mansoni infection in mice depleted of thymus-dependent lymphocytes. II. Pathology and altered pathogenesis. American Journal of Pathology 71, 207–18.Google ScholarPubMed
Byram, J. E., Doenhoff, M. J., Musallam, R., Brink, L. H. & Von Lichtenberg, F. (1979). Schistosoma mansoni infections in T-cell deprived mice, and the ameliorating effect of administering homologous chronic infection serum. II. Pathology. American Journal of Tropical Medicine and Hygiene 28, 274–85.CrossRefGoogle ScholarPubMed
Byram, J. E. & Von Lichtenberg, F. (1977). Altered schistosome granuloma formation in nude mice. American Journal of Tropical Medicine and Hygiene 26, 944–56.CrossRefGoogle ScholarPubMed
Carter, C. E. & Colley, D. G. (1978). An electrophoretic analysis of a Schistosoma mansoni soluble egg antigen preparation. Journal of Parasitology 64, 385–90.CrossRefGoogle ScholarPubMed
Carter, C. E. & Colley, D. G. (1979). Partial purification and characterization of Schistosoma mansoni soluble egg antigen with Con A-sepharose chromatography. Journal of Immunology 122, 2204–9.CrossRefGoogle ScholarPubMed
Cha, Y-N., Byram, J. E., Heine, H. S. & Bueding, E. (1980). Effect of Schistosoma mansoni infection on hepatic drug-metabolizing capacity of athymic nude mice. American Journal of Tropical Medicine and Hygiene 29, 234–8.CrossRefGoogle ScholarPubMed
Cheever, A. W. (1968). Conditions affecting the accuracy of potassium hydroxide digestion techniques for counting Schistosoma mansoni eggs in tissues. Bulletin of the World Health Organization 39, 328–31.Google ScholarPubMed
Chin, J., Sato, P. A. & Mann, J. M. (1990). Projections of HIV infections and AIDS cases to the year 2000. Bulletin of the World Health Organization 68, 111.Google Scholar
Doenhoff, M., Harrison, R., Sabah, A., Murare, H., Dunne, D. W. & Hassounah, O. (1982). Schistosomiasis in the immunosuppressed host: studies on the host-parasite relationship of Schistosoma mansoni and S. bovis in T-cell-deprived and hydrocortisone-treated mice. In Animal Models in Parasitology, (ed. Owen, D. G.) pp. 155169. London: Macmillan.CrossRefGoogle Scholar
Doenhoff, M. J., Musallam, R., Bain, J. & McGregor, A. (1978). Studies on the host–parasite relationship in Schistosoma mansoni-infected mice: the immunological dependence of parasite egg excretion. Immunology 35, 771–8.Google ScholarPubMed
Doenhoff, M. J., Musallam, R., Bain, J. & McGregor, A. (1979). Schistosoma mansoni infections in T-cell deprived mice, and the ameliorating effect of administering homologous chronic infection serum. I. Pathogenesis. American Journal of Tropical Medicine and Hygiene 28, 260–73.CrossRefGoogle ScholarPubMed
Doenhoff, M. J., Pearson, S., Dunne, D. W., Bickle, Q., Lucas, S., Bain, J., Musallam, R. & Hassounah, O. (1981). Immunological control of hepatotoxicity and parasite egg excretion in Schistosoma mansoni infections: stage specificity of the reactivity of immune serum in T-cell deprived mice. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 4153.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Dunne, D. W. & Bickle, Q. (1987). Identification and characterization of a polysaccharide-containing antigen from Schistosoma mansoni eggs which cross-reacts with the surface of schistosomula. Parasitology 94, 255–68.CrossRefGoogle ScholarPubMed
Dunne, D. W., Lucas, S., Bickle, Q., Pearson, S., Madgwick, L., Bain, J. & Doenhoff, M. J. (1981). Identification and partial purification of an antigen (ω1) from Schistosoma mansoni eggs which is putatively hepatotoxic in T-cell deprived mice. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 5471.CrossRefGoogle Scholar
Epstein, W. L., Fukuyama, K., Danno, K. & Kwan-Wong, E. (1979). Granulomatous inflammation in normal and athymic mice infected with Schistosoma mansoni: an ultrastructural study. Journal of Pathology 127, 207–15.CrossRefGoogle ScholarPubMed
Fine, D. P., Buchanan, R. D. & Colley, D. G. (1973). Schistosoma mansoni infection in mice depleted of thymus-dependent lymphocytes. I. Eosinophilia and immunologic response to a schistosomal egg preparation. American Journal of Pathology 71, 193206.Google ScholarPubMed
Hamburger, J., Pelley, R. P. & Warren, K. S. (1976). Schistosoma mansoni soluble egg antigens: determination of the stage and species specificity of their serological reactivity by radioimmunoassay. Journal of Immunology 117, 1561–6.CrossRefGoogle ScholarPubMed
Harrison, J. D., Carter, C. E. & Colley, D. G. (1981). Immunoaffinity purification of Schistosoma mansoni soluble egg antigens. Journal of Immunology 122, 2210–17.CrossRefGoogle Scholar
Hillyer, G. V. & Climent, C. (1988). Acquired Immunodeficiency Syndrome (AIDS) and parasitic diseases in Puerto Rico. Boletin Asociacion Medica de Puerto Rico 80, 312–19.Google ScholarPubMed
Knauft, R. F. & Warren, K. S. (1969). The effect of calorie and protein malnutrition on the parasite and the host in acute murine schistosomiasis mansoni. Journal of Infection and Disease 120, 560–75.CrossRefGoogle Scholar
Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227, 680–5.CrossRefGoogle ScholarPubMed
Lichtenberg, Von F. (1964). Studies on granuloma formation. III. Antigen sequestrian and destruction in the schistosome pseudotubercle. American Journal of Pathology 45, 7593.Google Scholar
Lichtenberg, Von F. (1979). Experimental approaches to human schistosomiasis. American Journal of Tropical Medicine and Hygiene 26, 7987.CrossRefGoogle Scholar
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry 193, 265–75.CrossRefGoogle ScholarPubMed
Lucas, S., Musallam, R., Bain, J., Hassounah, O., Bickle, Q. & Doenhoff, M. (1980). The pathological effects of immunosuppression of Schistosoma mansoni-infected mice, with particular reference to survival and hepatotoxicity after thymectomy and treatment with anti-thymocyte serum, and treatment with hydrocortisone acetate. Transactions of the Royal Society of Tropical Medicine and Hygiene 74, 633–43.CrossRefGoogle ScholarPubMed
Mathew, R. C. & Boros, D. L. (1986). Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infections. Infection and Immunity 54, 820–6.CrossRefGoogle Scholar
McLaren, M. L., Lillywhite, J. E., Dunne, D. W. & Doenhoff, M. (1981). Serodiagnosis of human Schistosoma mansoni infections: enhanced sensitivity and specificity in ELISA using a fraction containing S. mansoni egg antigens ω1 and α1. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 72–9.CrossRefGoogle Scholar
Mott, K. E. & Dixon, H. (1982). Collaborative study on antigens for immunodiagnosis of schistosomiasis. Bulletin of the World Health Organization 60, 729–53.Google Scholar
Murare, H. M. & Doenhoff, M. J. (1987). Parasitological observations of S. bovis in normal and T-cell deprived mice. Parasitology 95, 507–16.CrossRefGoogle ScholarPubMed
Phillips, S. M., Reid, W. A., Doughty, B. L. & Bentley, A. G. (1980). The immunological modulation of morbidity in schistosomiasis. Studies in athymic mice and in vitro granuloma formation. American Journal of Tropical Medicine and Hygiene 29, 820–31.CrossRefGoogle ScholarPubMed
Pelley, R. P., Pelley, R. J., Hamburger, J., Peters, P. A. & Warren, K. S. (1976). Schistosoma mansoni soluble egg antigens. 1. Identification and purification of three antigens, and the employment of radioimmunoassay for their further characterization. Journal of Immunology 117, 1553–60.CrossRefGoogle ScholarPubMed
Sherlock, S. (1983). Acute fatty liver of pregnancy and the microvesicular fat diseases. Gut 24, 265–9.CrossRefGoogle ScholarPubMed
Tuur, S. M., Macher, A. M., De Vinatea, M. L., Baird, J. K., Neafie, R., McGivney, R. K. & McKee, E. M. (1987). AIDS case for diagnosis. Military Medicine 152, M9–16.Google ScholarPubMed
Warren, K. S. (1975). Hepatosplenic schistosomiasis mansoni: an immunologic disease. Bulletin of the New York Academy of Medicine 51, 545–50.Google ScholarPubMed
Warren, K. S., Domingo, E. O. & Cowan, R. B. T. (1967). Granuloma formation around schistosome eggs as a manifestation of delayed hypersensitivity. American Journal of Pathology 51, 735–48.Google ScholarPubMed
Wray, W. T., Boulikas, V. P. & Hancock, R. (1981). Staining of proteins in polyacrylamide gels. Journal of Analytical Biochemistry 118, 197203.CrossRefGoogle ScholarPubMed
Zacharius, R. M., Zell, T. E., Morrison, J. H. & Woodlock, J. J. (1969). Glycoprotein staining following electrophoresis on acrylamide gels. Journal of Analytical Biochemistry 30, 148–52.CrossRefGoogle ScholarPubMed