Revista: | Memorias do Instituto Oswaldo Cruz |
Base de datos: | PERIÓDICA |
Número de sistema: | 000459457 |
ISSN: | 0074-0276 |
Autores: | Marin, Adriana A1 Juillard, Annette2 Katzin, Alejandro M1 Carvalho, Leonardo J.M3 Grau, Georges E.R2 |
Instituciones: | 1Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Sao Paulo. Brasil 2University of Sydney, Department of Pathology, Sydney, Nueva Gales del Sur. Australia 3Fundacao Oswaldo Cruz, Instituto Oswaldo Cruz, Rio de Janeiro. Brasil |
Año: | 2023 |
Volumen: | 118 |
País: | Brasil |
Idioma: | Inglés |
Tipo de documento: | Artículo |
Enfoque: | Experimental, aplicado |
Resumen en inglés | Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models. OBJECTIVE To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs. METHODOLOGY The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER). FINDINGS POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A. CONCLUSIONS POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis |
Disciplinas: | Medicina |
Palabras clave: | Parasitología, Inmunología, Paludismo encefálico, Moléculas de adhesión, Terpenos, Células endoteliales, Cerebro, Plasmodium falciparum |
Keyword: | Parasitology, Immunology, Cerebral malaria, Cell adhesion molecules, Terpenes, Endothelial cells, Brain, Plasmodium falciparum |
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