Disruption of Plasmodium falciparum Erythrocyte Rosettes by Standard Heparin and Heparin Devoid of Anticoagulant Activity

Johan Carlson Department of Immunology, Stockholm University, Department of Infectious Diseases, Akademiska Sjukhuset, Uppsala University, Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institutet, Research and Development, Immunobiology, Kabi AB, Department of Experimental Parasitology, Institut Pasteur, Medical Research Council Laboratories, Stockholm, Sweden

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Hans-Peter Ekre Department of Immunology, Stockholm University, Department of Infectious Diseases, Akademiska Sjukhuset, Uppsala University, Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institutet, Research and Development, Immunobiology, Kabi AB, Department of Experimental Parasitology, Institut Pasteur, Medical Research Council Laboratories, Stockholm, Sweden

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Helena Helmby Department of Immunology, Stockholm University, Department of Infectious Diseases, Akademiska Sjukhuset, Uppsala University, Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institutet, Research and Development, Immunobiology, Kabi AB, Department of Experimental Parasitology, Institut Pasteur, Medical Research Council Laboratories, Stockholm, Sweden

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Jurg Gysin Department of Immunology, Stockholm University, Department of Infectious Diseases, Akademiska Sjukhuset, Uppsala University, Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institutet, Research and Development, Immunobiology, Kabi AB, Department of Experimental Parasitology, Institut Pasteur, Medical Research Council Laboratories, Stockholm, Sweden

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Brian M. Greenwood Department of Immunology, Stockholm University, Department of Infectious Diseases, Akademiska Sjukhuset, Uppsala University, Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institutet, Research and Development, Immunobiology, Kabi AB, Department of Experimental Parasitology, Institut Pasteur, Medical Research Council Laboratories, Stockholm, Sweden

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Mats Wahlgren Department of Immunology, Stockholm University, Department of Infectious Diseases, Akademiska Sjukhuset, Uppsala University, Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institutet, Research and Development, Immunobiology, Kabi AB, Department of Experimental Parasitology, Institut Pasteur, Medical Research Council Laboratories, Stockholm, Sweden

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DOI:
https://doi.org/10.4269/ajtmh.1992.46.595
Volume/Issue:
Volume 46: Issue 5
Page(s):
595ā€“602
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We have studied the ability of heparin to disrupt spontaneous rosettes formed between Plasmodium falciparum-infected and uninfected red blood cells, which has been proposed to have importance in the pathogenesis of cerebral malaria. Substantial variation in this activity was found among six laboratory stains of P. falciparum. Rosettes formed by three of these strains were highly sensitive to heparin (50% disruption at 0.5ā€“25 Āµg/ml; 1 Āµg/ml corresponds to 0.15 IU/ml). The rosettes formed by two other strains showed a much lower sensitivity (50% disruption at 700ā€“2,500 Āµg/ml), while the rosettes formed by another strain were almost completely resistant to heparin (20% disruption at 6,500 Āµg/ml). The ability of heparin (65 or 650 Āµg/ml) to disrupt rosettes formed by 54 fresh Gambian isolates of P. falciparum also varied. Rosettes of 27 (50%) of the 54 isolates were disrupted to a significant degree (ā‰„ 15%), while rosettes of the other 27 isolates remained unaffected at the concentrations tested. Heparin was fractionated by molecular weight and/or affinity for antithrombin III. We found that its property of rosette disruption was associated, to some extent, with size (high molecular weight) but not with its anticoagulant potential (affinity for antithrombin III). A heparin fraction with low affinity for antithrombin III and one with combined high molecular weight and low affinity for antithrombin III were as effective at disrupting rosettes as standard heparin, while a chemically modified (N-acetylated) high molecular weight-heparin fraction, similarly devoid of anticoagulant activity, lacked strong anti-rosette potential. The heparin fractions with low affinity for antithrombin III and high molecular weight/low affinity for antithrombin III may prove to be useful in the treatment of severe P. falciparum malaria.
Copyright:
Copyright Ā© 1992 by The American Society of Tropical Medicine and Hygiene 1992
Published Online:
May 1992
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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