Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-23T00:48:04.815Z Has data issue: false hasContentIssue false
  • English
  • Français

Schistosomula, pre-adults and adults of Schistosoma mansoni ingest fluorescence-labelled albumin in vitro and in vivo: implication for a drug-targeting model

Published online by Cambridge University Press:  26 May 2010

M. C. HOLTFRETER ,
M. LOEBERMANN ,
E. FREI ,
D. RIEBOLD ,
D. WOLFF ,
G. HARTUNG ,
R. KINZELBACH  and
E. C. REISINGER
M. C. HOLTFRETER
Affiliation:
Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, University of Rostock, Ernst-Heydemann Strasse 6, 18057 Rostock, Germany
M. LOEBERMANN
Affiliation:
Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, University of Rostock, Ernst-Heydemann Strasse 6, 18057 Rostock, Germany
E. FREI
Affiliation:
Division of Molecular Toxicology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
D. RIEBOLD
Affiliation:
Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, University of Rostock, Ernst-Heydemann Strasse 6, 18057 Rostock, Germany
D. WOLFF
Affiliation:
Department of Haematology/Oncology, University Medical Center, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
G. HARTUNG
Affiliation:
Department for Medical Oncology/Hematology, Klinikum Oldenburg, Rahel-Straus-Strasse 10, 26133 Oldenburg, Germany
R. KINZELBACH
Affiliation:
Department of General and Systematic Zoology, Institute for Biosciences, University of Rostock, Universitätsplatz 2, 18055 Rostock, Germany
E. C. REISINGER*
Affiliation:
Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, University of Rostock, Ernst-Heydemann Strasse 6, 18057 Rostock, Germany
*
*Corresponding author: Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, University of Rostock Medical School, Ernst-Heydemann-Strasse 6, D-18057 Rostock, Germany. Tel: 0049 381 4947510. Fax: 0049 381 494 7509. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Objective. Bilharziosis is one of the most important helminthal infections in humans and is caused by blood flukes of the genus Schistosoma. Three different life stages of the parasite occur within the mammalian host: schistosomula located in the skin, pre-adults located in the lung and adult worms located in the portal venous system. Erythrocytes are a major source of nutrient supply for adults. However, sources of nutrition for the developing stages are still unclear. Methods. To investigate whether schistosomula, pre-adults and adults of Schistosoma mansoni ingest human serum albumin (HSA) in vitro, these life stages were incubated with aminofluorescein-labelled human serum albumin (Afl-HSA) for 5 h. To test the uptake of albumin in vivo, the albumin conjugate was given intravenously to S. mansoni infected NMRI mice 24 h before harvesting the 3 life stages. Results. In comparison to the control group schistosomula, pre-adults, and adults showed an accumulation of Afl-HSA within the oesophagus and intestinal caecum in vitro and in vivo. Conclusion. Our findings suggest that albumin seems to be a major source of energy supply for the early schistosomal life stages and an additive energy support for adult worms. Since albumin has been used successfully as a drug carrier for chemotherapeutic substances against malignant disorders, further studies will focus on albumin as a carrier for anthelminthics in a drug-targeting model.

Keywords

Schistosoma mansonischistosomulapre-adultsadultsingestionhuman serum albuminaminofluoresceindrug targeting
Type
Research Article
Information
Parasitology , Volume 137 , Issue 11 , September 2010 , pp. 1645 - 1652
Copyright
Copyright © Cambridge University Press 2010

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

Barros, L. A., Neves, R. H., De Moura, E. G. and Machado-Silva, J. R. (2009). Effects of low-protein diet on Schistosoma mansoni morphology visualized by morphometry and confocal laser scanning microscopy. Journal of Helminthology 83, 13–21.CrossRefGoogle ScholarPubMed
Bennett, M. W. and Caulfield, J. P. (1991). Schistosoma mansoni: ingestion of dextrans, serum albumin, and IgG by schistosomula. Experimental Parasitology 73, 52–61.Google Scholar
Bogers, J. J. P. M., Nibbeling, H. A. M., Van Marck, E. A. E. and Deeler, A. M. (1994). Immunofluorescent visualization of the excretory and gut system of Schistosoma mansoni by confocal laser scanning microscopy. The American Journal of Tropical Medicine and Hygiene 50, 612–619.Google Scholar
Bogitsh, B. J. (1989). Observations on digestion in schistosomes or “Blood and guts”. Transactions of the American Microscopical Society 108, 1–5.Google Scholar
Bolling, C., Graefe, T., Lübbing, C., Jankevicius, F., Uktveris, S., Cesas, A., Meyer-Moldenhauer, W. H., Starkmann, H., Weigel, M., Burk, K. and Hanauske, A. R. (2006). Phase II study of MTX-HSA in combination with Cisplatin as first line treatment in patients with advanced or metastatic transitional cell carcinoma. Investigational New Drugs 24, 521–527.Google Scholar
Clegg, J. A. (1965). In vitro cultivation of Schistosoma mansoni. Experimental Parasitology 16, 133–147.Google Scholar
Crabtree, J. E. and Wilson, R. A. (1980). Schistosoma mansoni: a scanning electron microscope study of the developing schistosomulum. Parasitology 81, 553–564.CrossRefGoogle ScholarPubMed
Delcroix, M., Sajid, M., Caffrey, C. R., Lim, K. C., Dvorak, J., Hsieh, I., Bahgat, M., Dissous, C. and McKerrow, J. H. (2006). A multienzyme network functions in intestinal protein digestion by a plathyhelminthic parasite. The Journal of Biological Chemistry 281, 39316–39329.CrossRefGoogle ScholarPubMed
El-Ridi, R., Ozaki, T., Inaba, T., Ito, M. and Kamiya, H. (1997). Schistosoma mansoni oviposition in vitro reflects worm fecundity in vivo: individual-, parasite age- and host-dependent variations. International Journal for Parasitology 27, 381–387.CrossRefGoogle ScholarPubMed
Fripp, P. J. (1967). The sites of (1–14C) glucose assimilation in Schistosoma haematobium. Comparative Biochemistry and Physiology 23, 893–898.Google Scholar
Furlong, S. T., Thibault, K. S. and Rogers, R. A. (1992). Fluorescent phospholipids preferentially accumulate in sub-tegumental cells of schistosomula of Schistosoma mansoni. Journal of Cell Science 103, 823–830.CrossRefGoogle ScholarPubMed
Halton, D. W. (1997). Nutritional adaptations to parasitism within the plathyhelminths. International Journal for Parasitology 27, 693–704.CrossRefGoogle Scholar
Hartung, G., Stehle, G., Sinn, H., Wunder, A., Schrenk, H. H., Heegers, S., Kranzle, M. E. L., Frei, E., Fiebig, H. H., Heene, D. L., Maier-Borst, W. and Queisser, W. (1999). Phase I trial of methotrexate-albumin in a weekly intravenous bolus regimen in cancer patients. Phase I study group of the Association for Medical Oncology of the German Cancer Society. Clinical Cancer Research 5, 753–759.Google Scholar
Kusel, J. R., Oliveira, F. A., Todd, M., Ronketti, F., Lima, S. F., Mattos, A. C. A., Reis, K. T., Coelho, P. M. Z., Thornhill, J. A. and Ribeiro, F. (2006). The effects of drugs, ions, and poly-l-lysine on the excretory system of Schistosoma mansoni. Memórias do Instituto Oswaldo Cruz 101, 293–298.Google Scholar
Lademann, M., Burchard, G. D. and Reisinger, E. C. (2000). Schistosomiasis and travel medicine. European Journal of Medical Research 5, 405–410.Google ScholarPubMed
Lawrence, J. D. (1973). The ingestion of red blood cells by Schistosoma mansoni. The Journal of Parasitology 59, 60–63.Google Scholar
Miller, P. and Wilson, R. A. (1978). Migration of the schistosomula of Schistosoma mansoni from skin to the lungs. Parasitology 77, 281–302.CrossRefGoogle Scholar
Neves, R. H., Machado-Silva, J. R., Pelajo-Machado, M., Oliviera, S. A., Coutino, E. M., Lenzi, H. L. and Gomes, D. C. (2001). Morphological aspects of Schistosoma mansoni adult worms isolated from nourished and undernourished mice: a comparative analysis by confocal laser scanning microscopy. Memórias do Instituto Oswaldo Cruz 96, 1013–1016.CrossRefGoogle ScholarPubMed
Ramalho-Pinto, F. J., Gazzinelli, G., Howells, R. E., Mota-Santos, T. A., Figueiredo, E. A. and Pelliogrino, J. (1974). Schistosoma mansoni: defined medium for stepwise transformation of cercariae to schistosomula in vitro. Experimental Parasitology 50, 369–383.Google Scholar
Sato, H., Kusel, J. R. and Thornhill, J. (2004). Excretion of fluorescent substrates of mammalian multidrug resistance-associated protein (MRP) in the Schistosoma mansoni excretory system. Parasitology 128, 43–52.Google Scholar
Silva, L. M., Menezes, R. M. C., Andrade de Oliveira, S. and Andrade, Z. A. (2003). Chemotherapeutic effect on larval stages of Schistosoma mansoni during infection and re-infection of mice. Revista da Sociedade Brasileira de Medicina Tropical 36, 335–341.CrossRefGoogle ScholarPubMed
Skelly, P. J., Tielens, A. G. M. and Shoemaker, C. B. (1998). Glucose transport and metabolism in mammalian stage schistosomes. Parasitology Today 14, 402–406.Google Scholar
Tan, H. H. C., Thornhill, J. A., Al-Adhami, B. H., Akhkha, A. and Kusel, J. R. (2003). A study of the effect of surface damage on the uptake of Texas Red-BSA by schistosomula of Schistosoma mansoni. Parasitology 126, 235–240.Google Scholar
Uglem, G. L. and Read, C. P. (1976). Sugar transport and metabolism in Schistosoma mansoni. The Journal of Parasitology 61, 390–397.Google Scholar
Vis, A. N., van der Gaast, A., van Rhijn, B. W., Catsburg, T. K., Schmidt, T. C. and Mickisch, G. H. J. (2002). A phase II trial of methotrexate-human serum albumin (MTX-HSA) in patients with metastatic renal cell carcinoma who progressed under immunotherapy. Cancer Chemotherapy and Pharmacology 49, 342–345.Google ScholarPubMed
Wippersteg, V., Ribeiro, F., Liedtke, S., Kusel, J. R. and Grevelding, C. G. (2003). The uptake of Texas Red-BSA in the excretory system of schistosomes and its colocalisation with ER60 promotor-induced GFP in transiently transformed adult males. International Journal for Parasitology 33, 1139–1143.CrossRefGoogle Scholar
Wolff, D., Frei, E., Hofmeister, N., Steiner, B., Kleine, H. D., Junghanss, C., Sievert, K., Terpe, H., Schrenk, H. H., Freund, M. and Hartung, G. (2006). Methotrexate-albumin and aminopterin-albumin effectively prevent experimental acute graft-versus-host disease. Transplantation 82, 527–533.Google Scholar
Wunder, A., Müller-Ladner, U., Stelzer, E. H., Funk, J., Neumann, E., Stehle, G., Pap, T., Sinn, H., Gay, S. and Fiehn, C. (2003). Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. Journal of Immunology 170, 4793–4801.Google Scholar