Soluble factors from Plasmodium falciparum-infected erythrocytes induce apoptosis in human brain vascular endothelial and neuroglia cells.
The severity of malaria is multi-factorial. It is associated with parasite-induced alteration in pro-inflammatory and anti-inflammatory cytokine and chemokine levels in host serum and cerebrospinal fluid. It is also associated with sequestration and cytoadherence of parasitized erythrocytes (pRBCs) in post-capillary venules and blood-brain barrier (BBB) dysfunction. The role of these factors in development of vascular injury and tissue damage in malaria patients is unclear. While some studies indicate a requirement for pRBC adhesion to vascular endothelial cells (ECs) in brain capillaries to induce apoptosis and BBB damage, others show no role of apoptosis resulting from adhesion of pRBC to EC. In the present study, the hypothesis that soluble factors from Plasmodium falciparum-infected erythrocytes induce apoptosis in human brain vascular endothelial (HBVEC) and neuroglia cells (cellular components of the BBB) was tested. Apoptotic effects of parasitized (pRBC) and non-parasitized erythrocyte (RBC) conditioned medium on HBVEC and neuroglia cells were determined in vitro by evaluating nuclear DNA fragmentation (TUNEL assay) in cultured cells. Soluble factors from P. falciparum-infected erythrocytes in conditioned medium induced extensive DNA fragmentation in both cell lines, albeit to a greater extent in HBVEC than neuroglia, indicating that extended exposure to high levels of these soluble factors in serum may be associated with vascular, neuronal and tissue injury in malaria patients.
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310, USA.
Nana O
NO
Wilson
Ming-Bo
MB
Huang
Winston
W
Anderson
Vincent
V
Bond
Michael
M
Powell
Winston E
WE
Thompson
Henry B
HB
Armah
Andrew A
AA
Adjei
Richard
R
Gyasi
Yao
Y
Tettey
Jonathan K
JK
Stiles
D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000469:parasitology; D004730:Endothelium, Vascular / Q000166:cytology*; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism / Q000469:parasitology; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000472:pathogenicity*