Heme-Mediated Induction of CXCL10 and Depletion of CD34+ Progenitor Cells Is Toll-Like Receptor 4 Dependent

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.     

Soybean dry matter and N accumulation responses to flooding stress, N sources and hypoxia

Soybean (Glycine max [L.] Merr.) is generally considered sensitive to flooding stress. Data on relative sensitivities of biomass accumulation and N2 fixation to flooding stress, however, are limited. Additionally, it is not clear why plants dependent on N2 fixation appear to be more flood-sensitive than plants supplemented with inorganic N. This study evaluated the response to flooding and N source of biomass and N accumulation in various soybean genotypes. Soybean plants were grown in a potting mixture in a greenhouse and flooded for 21 d in degassed nutrient solution. An additional experiment evaluated root hypoxia by exposing roots of plants to a gas mixture supplying 1.5 kPa pO2. Dry matter and N were determined at various times following the initiation of flood or low O2 treatment. In all experiments, N2 fixation was more sensitive to flooding than was biomass accumulation. The decrease in N2 fixation occurred faster (within 7 d of flooding) than the decrease in biomass (within 14-21 d), and the decrease in N2 fixation was more pronounced than the decrease in biomass. Addition of nitrate decreased flood sensitivity relative to plants dependent on N2 fixation. Plant response to hypoxia was similar to flooding. Biomass of plants with roots exposed to 1.5 kPa pO2 was decreased by 34% when dependent on N2 fixation and 12% when supplemented with nitrate. Collectively, the data indicate that decreased soybean growth under flooding is a result of decreased N2 fixation and that supplementation of soybean plants with nitrate may improve their tolerance to flooding relative to those relying on N2 fixation.Keywords: Soybean, Glycine max, flooding stress, hypoxia, N source, nitrogen fixation.