Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-24T03:23:02.230Z Has data issue: false hasContentIssue false

Schistosoma mansoni: morphology and ultrastructure of adult worms recovered from cyclosporin A-treated mice

Published online by Cambridge University Press:  06 April 2009

G. H. Munro
Affiliation:
Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA
D. J. McLaren
Affiliation:
Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA

Summary

Cyclosporin A administered to Schistosoma mansoni-infected mice at around day 20 of infection reduces the worm burden by > 60%, as assessed by portal perfusion on days 28 and 86. Those worms recovered at perfusion have been examined by light and electron microscopy for drug-induced changes in morphology. Gross parasite damage was characterized by massive bolus formation and subsequent herniation of the gut. This event was attributed to the abnormal accumulation of crystalline structures in the lumen; the crystals were closely associated with lipid droplets, and were shown by X-ray micro-analysis to contain iron. Such crystals were seen only rarely in the intestines of control worms, but they too gave small iron peaks when examined by X-ray micro-analysis. In some drug-treated worms the caecal epithelium had ruptured, thereby releasing luminal contents throughout the worm body. In addition, herniations of the gut were seen protruding through the tegument causing surface deformation and disruption of tegumental and parenchymal tissues. The structural integrity of the worm was ultimately compromised allowing access to cytotoxic effector cells of the host. The combined effects of drug action and cellular cytotoxicity presumably account for the very significant levels of worm killing achieved by CsA treatment of the host.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1990

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

Borel, J. F., Feurer, C., Gubler, H. V. & Stalehin, H. (1976). Biological effects of cyclosporin A: a new antilymphocytic agent. Agents and Actions 6, 468–75.Google Scholar
Bout, D., Deslee, D. & Capron, A. (1984 a). Protection against schistosomiasis produced by cyclosporin A. American Journal of Tropical Medicine and Hygiene 33, 185–6.Google Scholar
Bout, D., Deslee, D. & Capron, A. (1986). Antischistosomal effect of cyclosporin A: cure and prevention of mouse and rat schistosomiasis mansoni. Infection and Immunity 52, 823–7.Google Scholar
Bout, D., Haque, A. & Capron, A. (1984 b). Filaricidal effects of cyclosporin A against Dipetalonema viteae in Mastomys natalensis. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 670–1.Google Scholar
Bueding, E., Hawkins, J. & Cha, Y. N. (1981). Antischistosomal effects of cyclosporin A. Agents and Actions 11, 380–3.Google Scholar
chapell, C.L,&Dresden, M.H.(1987). SchistOSOtnamansoni: proteinase activity of ‘hemoglobinase’ fromthe digestive tract of adult worms.Experimental Parasitology 61, 160–7.Google Scholar
Chappell, L. H., Thomson, A. W., Barker, G. C. & Smith, S. W. G. (1987). Dosage, timing and route of administration of cyclosporin A and non-immunosuppressive derivatives of dihydrocyclosporin A and cyclosporin C against Schistosoma mansoni in vivo and in vitro. Antimicrobial Agents and Chemotherapy 31, 1567–71.Google Scholar
Davis, A. H., Nanduri, j.,&Watson, D.c.(1987). Cloning and gene expression of Schistosoma mansoni protease. Journal of Biological Chemistry 262, 12851–5.Google Scholar
Elsaghier, A. A. F., Knopf, P. M., Mitchell, G. F.,&Mclaren, D.j. (1989). Schistosoma mansoni: evidencethat ‘nonpermissiveness’in 129/Ola mice involves worm relocation and attrition in the lungs. Parasitology 99, 365–75.Google Scholar
Harnett, w. (1988). The anthelmintic action of praziquantel. Parasitology Today 4, 144–6.Google Scholar
Hashiguchi, Y. & Okamura, Y. (1988). The effects of cyclosporin A on the course of Paragonimus miyazakii infection in rats. Journal of Helminthology 62, 251–6.Google Scholar
Hess, A. D., Esa, A. H. & Colombani, P. M. (1988). Mechanisms of action of cyclosporine: effect on cells of the immune system and on subcellular events in T cell activation. Transplantation Proceedings 20, Suppl. 2yes, 2940.Google Scholar
Karnovsky, M.j. (1965). A formaldehyde-glutaraldehyde fixative of high molality for use in electron microscopy. Journal of Cell Biology 27, 137A.Google Scholar
Hockley, D.j. (1973). Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercariae to adult worm.InternationalJournal for Parasitology 3, 1325CrossRefGoogle ScholarPubMed
Lawrence, j.D. (1973). The ingestion of red blood cells by Schistosoma mansoni. Journal of Parasitology 59, 60–3Google Scholar
Mehlhorn, H., Becker, B., Andrews, P., Thomas, H. & Frenkel, j.K. (1981). In vivo and in vitro experiments on the effects of praziquantel on Schistosoma mansoni. Arzneimittelforschung 31, 544–54.Google Scholar
Munro, G.H.&Mclaren, D.J. (1990). Toxkity of cyclosporin A (CsA) against developmental stages of Schistosoma mansoni in mice. Parasitology 100, 2934CrossRefGoogle ScholarPubMed
Nickell, S. P., Scheibel, L. W. & Cole, G. A. (1982). Inhibition by cyclosporin A of rodent malaria in vivo and human malaria in vitro. Infection and Immunity 37, 1093–100.Google Scholar
Nilsson, L. A., Lindblad, R., Olling, S. & Ouchterlony, O. (1985). The effect of cyclosporin A on the course of murine infection by Schistosoma mansoni. Parasite Immunology 7, 1927.Google Scholar
Smith, S. W. G., Chappell, L. H., Thomson, A. W., Macgowan, A. G. & Simpson, A. J. G. (1988). Prophylactic and therapeutic effects of ciclosporin A in murine Schistosomiasis mansoni: studies on bisexual and unisexual infections and the hepatic inflammatory response. International Archives of Allergy and Applied Immunology 85, 174–9.CrossRefGoogle ScholarPubMed
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, 695700.Google Scholar
Thommen-Scott, K. (1981). Antimalarial activity of cyclosporin A. Agents and Actions 11, 770–3.Google Scholar
Zahner, H. & Schultheiss, K. (1987). Effect of cyclosporin A and some derivatives in Litomosoides carinii-infected Mastomys natalensis. Journal of Helminthology 61, 282–90.Google Scholar