In Vivo Imaging of the Buccal Mucosa Shows Loss of the Endothelial Glycocalyx and Perivascular Hemorrhages in Pediatric Plasmodium falciparum Malaria
| Autor: | John Lusingu, Thor G. Theander, Rasmus Reinhold Paulsen, Eric Lyimo, Casper Hempel, AM Efunshile, Alphaxard Manjurano, Thomas Ramsing, Lars Emil Haslund, Christian W. Wang, Jørgen A. L. Kurtzhals, Victor A. Makene |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Endothelium Plasmodium falciparum Immunology Incident dark field imaging Image analyses Microbiology Microcirculation Endothelial activation Glycocalyx Pathogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine SDG 3 - Good Health and Well-being parasitic diseases Hyaluronic acid medicine Host Response and Inflammation biology medicine.disease biology.organism_classification Endothelial glycocalyx Malaria 030104 developmental biology Infectious Diseases medicine.anatomical_structure chemistry Glycocalyx shedding Parasitology 030217 neurology & neurosurgery |
| Zdroj: | Infect Immun Lyimo, E, Haslund, L E, Ramsing, T, Wang, C W, Efunshile, A M, Manjurano, A, Makene, V, Lusingu, J, Theander, T G, Kurtzhals, J A L, Paulsen, R & Hempel, C 2020, ' In vivo imaging of the buccal mucosa shows loss of the endothelial glycocalyx and perivascular hemorrhages in pediatric Plasmodium falciparum malaria ', Infection and Immunity, vol. 88, no. 3, e00679-19 . https://doi.org/10.1128/iai.00679-19 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00679-19 |
| Popis: | Severe malaria is mostly caused by Plasmodium falciparum, resulting in considerable, systemic inflammation and pronounced endothelial activation. The endothelium forms an interface between blood and tissue, and vasculopathy has previously been linked with malaria severity. We studied the extent to which the endothelial glycocalyx that normally maintains endothelial function is involved in falciparum malaria pathogenesis by using incident dark-field imaging in the buccal mucosa. This enabled calculation of the perfused boundary region, which indicates to what extent erythrocytes can permeate the endothelial glycocalyx. The perfused boundary region was significantly increased in severe malaria patients and mirrored by an increase of soluble glycocalyx components in plasma. This is suggestive of a substantial endothelial glycocalyx loss. Patients with severe malaria had significantly higher plasma levels of sulfated glycosaminoglycans than patients with uncomplicated malaria, whereas other measured glycocalyx markers were raised to a comparable extent in both groups. In severe malaria, the plasma level of the glycosaminoglycan hyaluronic acid was positively correlated with the perfused boundary region in the buccal cavity. Plasma hyaluronic acid and heparan sulfate were particularly high in severe malaria patients with a low Blantyre coma score, suggesting involvement in its pathogenesis. In vivo imaging also detected perivascular hemorrhages and sequestering late-stage parasites. In line with this, plasma angiopoietin-1 was decreased while angiopoietin-2 was increased, suggesting vascular instability. The density of hemorrhages correlated negatively with plasma levels of angiopoietin-1. Our findings indicate that as with experimental malaria, the loss of endothelial glycocalyx is associated with vascular dysfunction in human malaria and is related to severity. |
| Databáze: | OpenAIRE |
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