Open AccessVascular endothelial cells cultured from patients with cerebral or uncomplicated malaria exhibit differential reactivity to TNF
Author(s) -
Wassmer Samuel Crocodile,
Moxon Christopher Alan,
Taylor Terrie,
Grau Georges Emile,
Molyneux Malcolm Edward,
Craig Alister Gordon
Publication year - 2011
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2010.01528.x
Subject(s) - cerebral malaria , biology , malaria , tumor necrosis factor alpha , stimulation , ex vivo , plasmodium falciparum , endothelial stem cell , immunology , in vivo , downregulation and upregulation , endothelial activation , inflammation , in vitro , endocrinology , biochemistry , microbiology and biotechnology , gene
Summary Plasmodium falciparum malaria is a major cause of morbidity and mortality in African children, and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. We studied the ex vivo responsiveness of microvascular endothelial cells to pro‐inflammatory stimulation and compared the findings between CM and UM patients. In patients with fatal disease we compared the properties of vascular endothelial cells cultured from brain tissue to those cultured from subcutaneous tissue, and found them to be very similar. We then isolated, purified and cultured primary endothelial cells from aspirated subcutaneous tissue of patients with CM (EC CM ) or UM (EC UM ) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro , EC CM displayed a significantly higher capacity to upregulate ICAM‐1, VCAM‐1 and CD61 and to produce IL‐6 and MCP‐1 but not RANTES compared with EC UM . The shedding of endothelial microparticles, a recently described parameter of severity in CM, and the cellular level of activated caspase‐3 were both significantly greater in EC CM than in EC UM . These data suggest that inter‐individual differences in the endothelial inflammatory response to TNF may be an additional factor influencing the clinical course of malaria.