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Patterns of haemozoin accumulation in tissue

Published online by Cambridge University Press:  06 April 2009

A. D. Sullivan
Affiliation:
Department of Epidemiology, University of Michigan School of Public Health, 109 Observatory Street, Ann Arbor, Michigan 48109, USA
I. Ittarat
Affiliation:
Department of Epidemiology, University of Michigan School of Public Health, 109 Observatory Street, Ann Arbor, Michigan 48109, USA
S. R. Meshnick
Affiliation:
Department of Epidemiology, University of Michigan School of Public Health, 109 Observatory Street, Ann Arbor, Michigan 48109, USA

Summary

A sensitive fluorometric method for assaying malarial pigment, haemozoin, has been developed and used to determine the haemozoin content of blood and tissue samples. Plasmodium falciparum rings and trophozoites were found to contain 23 and 339 ng haemozoin/106 parasitized red blood cells (PRBCs), respectively. Unsynchronized Plasmodium berghei NK65 or ANKA parasites from infected mice contained 27 and 61 ng haemozoin/106 PRBCs, respectively. An exponential accumulation of haemozoin within 18 days after infection was demonstrated in liver and spleen tissue, representing up to 0·2% of the tissue by wet weight by day 18. Histology indicated that the accumulation occurred predominantly in the tissue monocytes. In the brain, the levels of haemozoin after 8 days of infection were considerably lower than they were in the liver or spleen, and most of the pigment appeared to be that present inside parasitized red blood cells. CBA/Ca mice infected with P. berghei ANKA (a cerebral malaria model) had significantly higher amounts of haemozoin in the brain than did ICR mice infected with P. berghei NK65. Thus, haemozoin levels in tissue increase with the duration of infection, and its presence may be associated with cerebral pathology.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1996

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References

REFERENCES

Altman, P. L. & Dittmer, D. S. (1974). Biology Data Book, Vol. 3, 2nd Edn.Bethesda: Federation of American Societies for Experimental Biology.Google Scholar
Asawamahasakda, W., Ittarat, I., Chang, C., McElroy, P. & Meshnick, s. R. (1994). Effects of antimalarials and protease inhibitors on plasmodial hemozoin production. Molecular and Biochemical Parasitology 67, 183–91.CrossRefGoogle ScholarPubMed
Balla, G., Vercellotti, G. M., Muller-Eberhard, U., Eaton, J. & Jacob, H. S. (1991). Exposure of endothelial cells to free heme potentiates damage mediated by granulocytes and toxic oxygen species. Laboratory Investigation 64, 648–55.Google ScholarPubMed
Balla, J., Jacob, H., Balla, G., Nath, K., Eaton, J. & Vercellotti, G. (1993). Endothelial-cell heme uptake from heme proteins: Induction of sensitization and desensitization to oxidant damage. Proceedings of the National Academy of Sciences, USA 90, 9285–9.CrossRefGoogle ScholarPubMed
Bradford, M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding. Analytical Biochemistry 72, 248–54.CrossRefGoogle ScholarPubMed
Boonpucknavig, V. & Boonpucknavig, S. (1988). Histopathology of malaria. In Malaria: Principles and Practice of Malariology, vol. 1 (ed. Wernsdorfer, W. & McGregor, I.). London: Churchill Livingstone.Google Scholar
Carotenuto, P., Pontesilli, O., Cambier, J. C. & Hayward, A. R. (1986). Desferoxamine blocks IL 2 receptor expression on human T lymphocytes. Journal of Immunology 136, 2342–7.CrossRefGoogle ScholarPubMed
Chou, A. C. & Fitch, C. D. (1993). Control of heme polymerase by chloroquine and other derivatives. Biochemical and Biophysical Research Communications 195, 422–7.CrossRefGoogle Scholar
Cynshi, O., Shimonaka, Y., Higuchi, M., Imai, N., Suzuki, H., Togashi, M., Okamoto, M. T. & Hirashima, K. (1990). Effects of recombinant human erythropoietin on haemolytic anaemia in mice. British Journal of Haematology 76, 414–19.CrossRefGoogle ScholarPubMed
Dexter, D. T., Sian, J., Jenner, P. & Marsden, C. D. (1993). Implications of alterations in trace element levels in brain in Parkinson's disease and other neurological disorders affecting the basal ganglia. Advances in Neurology 60, 273–81.Google ScholarPubMed
Dorn, A., Stoffel, R., Matile, H., Bubendorf, A. & Ridley, R. G. (1995). Malaria haemozoin/β-haematin supports haem polymerization in the absence of protein. Nature, London 374, 269–71.CrossRefGoogle Scholar
Egan, T. J., Ross, D. C. & Adams, P. A. (1994). Quinoline anti-malarial drugs inhibit spontaneous formation of β-haematin (malaria pigment). FEBS Letters 352, 54–7.CrossRefGoogle ScholarPubMed
Fiori, P. L., Rapelli, P., Mirkarimi, S. N., Ginsburg, H., Cappuccinelli, p. & Turrini, F. (1993). Reduced microcidal and anti-tumour activities of human monocytes after ingestion of Plasmodium falciparum-infected red blood cells. Parasite Immunology 15, 647–55.CrossRefGoogle Scholar
Fitch, C. D. & Kanjananggulpan, P. (1987). The State of ferriprotoporphyrin IX in malaria pigment. Journal of Biological Chemistry 262, 15552–5.CrossRefGoogle ScholarPubMed
Galbraith, R. M., Faulk, W. P., Galbraith, G. M. P., Holbrook, T. W. & Bray, R. S. (1980). The human materno-foetal relationship in malaria: I. Identification of pigment and parasites in the placenta. Transactions of the Royal Society of Tropical Medicine and Hygiene 74, 5260.CrossRefGoogle ScholarPubMed
Grau, G. E., Fajardo, L. F., Piguet, P. F., Allet, B., Lambert, P. H. & Vasalli, P. (1987). Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237, 1210–12.CrossRefGoogle ScholarPubMed
Hara, H. & Ogawa, M. (1976). Erythropoietic precursors in mice with phenylhydrazine-induced anaemia. American Journal of Haematology 1, 453–8.CrossRefGoogle Scholar
Harrison, G. (1978). Mosquitoes, Malaria, and Man: A History of the Hostilities Since 1880. New York: E. P. Dutton.Google Scholar
Howells, R. E., Peters, W. & Thomas, A. (1968). The chemotherapy of rodent malaria. III. Host-parasite relationships part 3: The relationship between haemozoin formation and age of the host cell. Annals of Tropical Medicine and Parasitology 62, 267–71.CrossRefGoogle Scholar
Jenner, P. (1994). Oxidative damage in neurodegenerative disease. Lancet 344, 796–8.CrossRefGoogle ScholarPubMed
Jesberger, J. A. & Richardson, J. S. (1991). Oxygen free radicals and brain dysfunction. International Journal of Neuroscience 57, 117.CrossRefGoogle ScholarPubMed
Lambros, C. & Vanderburg, J. P. (1979). Synchronization of Plasmodium falciparum erythrocytic stages in culture. Journal of Parasitology 65, 418–20.CrossRefGoogle ScholarPubMed
Lawrence, C. & Olson, J. A. (1986). Birefringent hemozoin identifies malaria. American Journal of Clinical Pathology 86, 360–3.CrossRefGoogle ScholarPubMed
MacCallum, D. K. (1969). Time sequence study on the hepatic system of malaria-infected hamsters. Journal of the Reticuloendothelial Society 6, 232–52.Google Scholar
Morakote, N. & Justus, D. E. (1988). Immunosuppression in malaria: effect of haemozoin produced by Plasmodium berghei and Plasmodium falciparum. International Archives of Allergy and Applied Immunology 86, 2834.CrossRefGoogle ScholarPubMed
Orjih, A. U. & Fitch, C. D. (1993). Haemozoin productioi by Plasmodium falciparum: variation with strain and exposure to chloroquine. Biochimica et Biophysica Acta 1157, 270–4.CrossRefGoogle ScholarPubMed
Pichyangkul, S., Saengkrai, P. & Webster, H. K. (1994). Plasmodium falciparum pigment induces monocytes to release high levels of tumor necrosis factor-α and interleukin-1β. American Journal of Tropical Medicine and Hygiene 5, 430–5.CrossRefGoogle Scholar
Polson, R. J., Jenkins, R., Lombard, M., Williams, A. C., Roberts, S., Nouri-Aria, K., Williams, R. & Bomford, A. (1990). Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine. Immunology 71, 176–81.Google ScholarPubMed
Schalm, O. W., Jain, N. C. & Carroll, E. J. (1975). Veterinary Haematology, 3rd Edn.Philadelphia: Lea & Febiger.Google Scholar
Schwartz, S., Dahl, J., Ellefson, M. & Ahlquist, D. (1983). The ‘HemoQuant’ test: a specific and quantitative determination of heme (haemoglobin) in faeces and other materials. Clinical Chemistry 29, 2061–7.CrossRefGoogle Scholar
Schwarzer, E., Turrini, F., Ulliers, D., Giribaldi, G., Ginsburg, H. & Arese, P. (1992). Impairment of macrophage functions after ingestion of Plasmodium falciparum-infected erythrocytes of isolated malarial pigment. Journal of Experimental Medicine 176, 1033–41.CrossRefGoogle ScholarPubMed
Schwarzer, E., Turrini, F., Giribaldi, G., Cappadoro, M. & Arese, P. (1993). Phagocytosis of P. falciparum malarial pigment haemozoin by human monocytes inactivates monocyte protein kinase C. Biochimica et Biophysica Acta 1181, 51–4.CrossRefGoogle ScholarPubMed
Silamut, K. & White, N. J. (1993). Relation of the stage of parasite development in the peripheral blood to prognosis in severe falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 87, 436–43.CrossRefGoogle ScholarPubMed
Slater, A. F. G. & Cerami, A. (1992). Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature, London 355, 167–9.CrossRefGoogle ScholarPubMed
Slater, A. F. G., Swiggard, W. J., Orton, B. R., Flitter, W. D., Goldberg, D. E., Cerami, A. & Henderson, G. B. (1991). An iron-carboxylate bond links the haem units of malaria pigment. Proceedings of the National Academy of Sciences, USA 88, 325–9.CrossRefGoogle ScholarPubMed
Thumbwood, C. M., Hunt, N. H., Cowden, W. B. & Clark, I. A. (1989). Anti-oxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. British Journal of Experimental Pathology 70, 293303.Google Scholar
Tracer, W. & Jensen, J. B. (1976). Human malaria parasites in continuous culture. Science 193, 673–5.Google Scholar
Youdim, M. B. H., Ben-Shachar, D., Eschel, G., Finberg, J. P. M. & Riederer, P. (1993). The neurotoxicity of iron and nitric oxide: relevance to the etiology of Parkinson's disease. Advances in Neurology 60, 259–66.Google Scholar