Heme-mediated induction of CXCL10 and depletion of CD34+ progenitor cells is toll-like receptor 4 dependent

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dc.contributor.author Dickinson-Copeland, C.M.
dc.contributor.author Wilson, N.O.
dc.contributor.author Liu, M.
dc.contributor.author Driss, A.
dc.contributor.author Salifu, H.
dc.contributor.author Adjei, A.A.
dc.contributor.author Wilson, M.
dc.contributor.author Gyan, B.
dc.contributor.author Oduro, D.
dc.contributor.author Badu, K.
dc.contributor.author Botchway, F.
dc.contributor.author Anderson, W.
dc.contributor.author Bond, V.
dc.contributor.author Bacanamwo, M.
dc.contributor.author Singh, S.
dc.contributor.author Stiles, J.K.
dc.date.accessioned 2017-10-26T08:28:40Z
dc.date.available 2017-10-26T08:28:40Z
dc.date.issued 2015
dc.identifier.other 10.1371/journal.pone.0142328
dc.identifier.uri http://ugspace.ug.edu.gh/handle/123456789/22210
dc.description.abstract Plasmodium falciparum infection can cause microvascular dysfunction, cerebral encephalopathy and death if untreated. We have previously shown that high concentrations of free heme, and C-X-C motif chemokine 10 (CXCL10) in sera of malaria patients induce apoptosis in microvascular endothelial and neuronal cells contributing to vascular dysfunction, blood-brain barrier (BBB) damage and mortality. Endothelial progenitor cells (EPC) are microvascular endothelial cell precursors partly responsible for repair and regeneration of damaged BBB endothelium. Studies have shown that EPC's are depleted in severe malaria patients, but the mechanisms mediating this phenomenon are unknown. Toll-like receptors recognize a wide variety of pathogen-associated molecular patterns generated by pathogens such as bacteria and parasites. We tested the hypothesis that EPC depletion during malaria pathogenesis is a function of heme-induced apoptosis mediated by CXCL10 induction and toll-like receptor (TLR) activation. Heme and CXCL10 concentrations in plasma obtained from malaria patients were elevated compared with non-malaria subjects. EPC numbers were significantly decreased in malaria patients (P < 0.02) and TLR4 expression was significantly elevated in vivo. These findings were confirmed in EPC precursors in vitro; where it was determined that heme-induced apoptosis and CXCL10 expression was TLR4- mediated. We conclude that increased serum heme mediates depletion of EPC during malaria pathogenesis. en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title Heme-mediated induction of CXCL10 and depletion of CD34+ progenitor cells is toll-like receptor 4 dependent en_US
dc.type Article en_US


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