Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study

Cerebral Malaria (CM), a severe complication in Plasmodium falciparum infection is classified as one of the main causes of mortality in malaria. The clinical outcome of CM, broadly varies from recovery to a lethal endpoint. Investigation of post-mortem brain tissue of CM patients demonstrates BBB...

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Main Authors:	Mohd Nasir, Mohd Hamzah, J. Chakravort, Srabasti
Format:	Conference or Workshop Item
Language:	English English
Published:	UTM 2019
Subjects:	QR180 Immunology
Online Access:	http://irep.iium.edu.my/75099/ http://irep.iium.edu.my/75099/1/Page%2025-Hamzah-IPSB2019.pdf http://irep.iium.edu.my/75099/2/Front-IPSB2019.pdf

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recordtype	eprints
spelling	iium-750992019-10-30T06:14:59Z http://irep.iium.edu.my/75099/ Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study Mohd Nasir, Mohd Hamzah J. Chakravort, Srabasti QR180 Immunology Cerebral Malaria (CM), a severe complication in Plasmodium falciparum infection is classified as one of the main causes of mortality in malaria. The clinical outcome of CM, broadly varies from recovery to a lethal endpoint. Investigation of post-mortem brain tissue of CM patients demonstrates BBB breakdown (microhaemorrhages) with loss of tight junction proteins (TJPs), occludin, claudin-5 and ZO-1 in endothelial cells. Interestingly, this was observed in vessels in the presence and in the absence of sequestered PRBC. This suggested the mobilisation of direct and indirect mechanisms following PRBC sequestration. In previous studies, the endothelial cell monolayer integrity was reduced when cocultured directly with PRBC. To investigate the indirect effect of sequestration to the BBB integrity, human brain endothelial cells (tHBEC) were first co-cultured with PRBC after which, the co-culture supernatant was harvested and analysed for the presence of candidate soluble factors and functional assays performed. Interestingly, analysis of the co-culture supernatant showed the induction of the ADAMTS family of protease, ADAMTS-4. In addition, differential regulation of ADAMTS-1 and the matrix metalloproteases (MMP) family proteases, MMP-2 and MMP-9 was observed. Treatment of freshly cultured tHBEC monolayer with the co-culture supernatant demonstrated up to 2-fold reduction in tHBEC monolayer integrity within 3 hours, measured using FITC-dextran permeability assay. This was accompanied by reduction in the TEER and the endothelial cell TJPs. We propose that endothelial cell derived proteases in the co-culture supernatants that are released as a result of interaction with PRBC, during sequestration; contribute to BBB breakdown in CM. UTM 2019-09-25 Conference or Workshop Item NonPeerReviewed application/pdf en http://irep.iium.edu.my/75099/1/Page%2025-Hamzah-IPSB2019.pdf application/pdf en http://irep.iium.edu.my/75099/2/Front-IPSB2019.pdf Mohd Nasir, Mohd Hamzah and J. Chakravort, Srabasti (2019) Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study. In: The 2nd International Postgraduate Symposium In Biotechnology 2019 (IPSB), 24-25 Sep 2019, Skudai Johor.
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	QR180 Immunology
spellingShingle	QR180 Immunology Mohd Nasir, Mohd Hamzah J. Chakravort, Srabasti Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study
description	Cerebral Malaria (CM), a severe complication in Plasmodium falciparum infection is classified as one of the main causes of mortality in malaria. The clinical outcome of CM, broadly varies from recovery to a lethal endpoint. Investigation of post-mortem brain tissue of CM patients demonstrates BBB breakdown (microhaemorrhages) with loss of tight junction proteins (TJPs), occludin, claudin-5 and ZO-1 in endothelial cells. Interestingly, this was observed in vessels in the presence and in the absence of sequestered PRBC. This suggested the mobilisation of direct and indirect mechanisms following PRBC sequestration. In previous studies, the endothelial cell monolayer integrity was reduced when cocultured directly with PRBC. To investigate the indirect effect of sequestration to the BBB integrity, human brain endothelial cells (tHBEC) were first co-cultured with PRBC after which, the co-culture supernatant was harvested and analysed for the presence of candidate soluble factors and functional assays performed. Interestingly, analysis of the co-culture supernatant showed the induction of the ADAMTS family of protease, ADAMTS-4. In addition, differential regulation of ADAMTS-1 and the matrix metalloproteases (MMP) family proteases, MMP-2 and MMP-9 was observed. Treatment of freshly cultured tHBEC monolayer with the co-culture supernatant demonstrated up to 2-fold reduction in tHBEC monolayer integrity within 3 hours, measured using FITC-dextran permeability assay. This was accompanied by reduction in the TEER and the endothelial cell TJPs. We propose that endothelial cell derived proteases in the co-culture supernatants that are released as a result of interaction with PRBC, during sequestration; contribute to BBB breakdown in CM.
format	Conference or Workshop Item
author	Mohd Nasir, Mohd Hamzah J. Chakravort, Srabasti
author_facet	Mohd Nasir, Mohd Hamzah J. Chakravort, Srabasti
author_sort	Mohd Nasir, Mohd Hamzah
title	Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study
title_short	Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study
title_full	Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study
title_fullStr	Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study
title_full_unstemmed	Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study
title_sort	activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study
publisher	UTM
publishDate	2019
url	http://irep.iium.edu.my/75099/ http://irep.iium.edu.my/75099/1/Page%2025-Hamzah-IPSB2019.pdf http://irep.iium.edu.my/75099/2/Front-IPSB2019.pdf
first_indexed	2023-09-18T21:46:16Z
last_indexed	2023-09-18T21:46:16Z
_version_	1777413470927454208

Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria: an in vitro study

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