Effects of sevuparin on rosette formation and cytoadherence of Plasmodium falciparum infected erythrocytes
| Autor: | Juntima Sritabal, Srisuda Keayarsa, Nattaporn Piaraksa, Arjen M. Dondorp, Rachanee Udomsangpetch, Chirapong Utaisin, Nicholas P. J. Day, Patima Sila, Kesinee Chotivanich, Prakaykaew Charunwatthana, Somporn Saiwaew, Nicholas J. White, Ronnatrai Ruengweerayut, Sue J. Lee, Anna Leitgeb, Rangsan Niramis, Emsri Pongponratn, Mats Wahlgren, Sasithon Pukrittayakamee |
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| Přispěvatelé: | Craig, A |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Plasmodium Erythrocytes Physiology Heparin Cell lcsh:Medicine Epithelium Animal Cells Interquartile range Red Blood Cells Medicine and Health Sciences Medicine Malaria Falciparum lcsh:Science Cells Cultured Protozoans Multidisciplinary biology Malarial Parasites Drugs Middle Aged Parasitic diseases Body Fluids 3. Good health Blood medicine.anatomical_structure Rosette formation Female Cellular Types Anatomy Research Article medicine.drug Adult Rosette Formation Adolescent Plasmodium falciparum Endothelial cells Blood groups Microbiology 03 medical and health sciences Parasite Groups parasitic diseases Cell Adhesion Humans Trophozoites Aged Pharmacology Blood Cells business.industry lcsh:R Organisms Endothelial Cells Biology and Life Sciences Epithelial Cells Cell Biology Tropical Diseases biology.organism_classification medicine.disease Parasitic Protozoans Malaria Biological Tissue 030104 developmental biology Adjunctive treatment Parasitology lcsh:Q Malarial parasites business Apicomplexa Blood Groups Red blood cells |
| Zdroj: | PLoS ONE, Vol 12, Iss 3, p e0172718 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0172718 |
| Popis: | In severe falciparum malaria cytoadherence of parasitised red blood cells (PRBCs) to vascular endothelium (causing sequestration) and to uninfected red cells (causing rosette formation) contribute to microcirculatory flow obstruction in vital organs. Heparin can reverse the underlying ligand-receptor interactions, but may increase the bleeding risks. As a heparin-derived polysaccharide, sevuparin has been designed to retain anti-adhesive properties, while the antithrombin-binding domains have been eliminated, substantially diminishing its anticoagulant activity. Sevuparin has been evaluated recently in patients with uncomplicated falciparum malaria, and is currently investigated in a clinical trial for sickle cell disease. The effects of sevuparin on rosette formation and cytoadherence of Plasmodium falciparum isolates from Thailand were investigated. Trophozoite stages of P. falciparum-infected RBCs (Pf-iRBCs) were cultured from 49 patients with malaria. Pf-iRBCs were treated with sevuparin at 37°C and assessed in rosetting and in cytoadhesion assays with human dermal microvascular endothelial cells (HDMECs) under static and flow conditions. The proportion of Pf-iRBCs forming rosettes ranged from 6.5% to 26.0% (median = 12.2%). Rosetting was dose dependently disrupted by sevuparin (50% disruption by 250 μg/mL). Overall 57% of P. falciparum isolates bound to HDMECs under static conditions; median (interquartile range) Pf-iRBC binding was 8.5 (3.0-38.0) Pf-iRBCs/1000 HDMECs. Sevuparin in concentrations ≥ 100 μg/mL inhibited cytoadherence. Sevuparin disrupts P. falciparum rosette formation in a dose dependent manner and inhibits cytoadherence to endothelial cells. The data support assessment of sevuparin as an adjunctive treatment to the standard therapy in severe falciparum malaria. |
| Databáze: | OpenAIRE |
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