Heme-Mediated Induction of CXCL10 and Depletion of CD34+ Progenitor Cells Is Toll-Like Receptor 4 Dependent
| Autor: | Carmen M. Dickinson-Copeland, Nana O. Wilson, Mingli Liu, Adel Driss, Hassana Salifu, Andrew A. Adjei, Michael Wilson, Ben Gyan, Daniel Oduro, Kingsley Badu, Felix Botchway, Winston Anderson, Vincent Bond, Methode Bacanamwo, Shailesh Singh, Jonathan K. Stiles |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0303 health sciences Multidisciplinary Adolescent 030306 microbiology Stem Cells lcsh:R Correction lcsh:Medicine Antigens CD34 Heme 3. Good health Cell Line Chemokine CXCL10 Toll-Like Receptor 4 03 medical and health sciences Case-Control Studies Child Preschool Humans Female lcsh:Q Malaria Falciparum Child lcsh:Science 030304 developmental biology |
| Zdroj: | PLoS ONE, Vol 11, Iss 1, p e0147460 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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 (P0.02) 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. |
| Databáze: | OpenAIRE |
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