Hyperglycaemia augments lipopolysaccharide-induced reduction in rat and human macrophage phagocytosis via the endoplasmic stress-C/EBP homologous protein pathway.

BACKGROUND: Macrophage phagocytosis constitutes an essential part of the host defence against microbes and the resolution of inflammation. Hyperglycaemia during sepsis is reported to reduce macrophage function, and thus, potentiate inflammatory deterioration. We investigated whether high-glucose concentrations augment lipopolysaccharide-induced reduction in macrophage phagocytosis via the endoplasmic stress-C/EBP homologous protein (CHOP) pathway using animal and laboratory investigations. METHODS: Peritoneal macrophages of artificially ventilated male Wistar rats, divided into four groups based on target blood glucose concentrations achieved by glucose administration with or without lipopolysaccharide, were obtained after 24 h. Human macrophages were also cultured in normal or high glucose with or without lipopolysaccharide exposure for 72 h. Changes in the phagocytic activity, intranuclear CHOP expression, and intracellular Akt phosphorylation status of macrophages were evaluated. These changes were also evaluated in human macrophages after genetic knock-down of CHOP by specific siRNA transfection or resolvin D2 treatment. RESULTS: Lipopolysaccharide impaired phagocytosis, increased intranuclear expression of CHOP, and inhibited Akt phosphorylation in both rat peritoneal and human macrophages. Hyperglycaemic glucose concentrations augmented these changes. Genetic knock-down of CHOP restored phagocytic ability and Akt phosphorylation in human macrophages. Furthermore, resolvin D2 co-incubation restored the inhibited phagocytosis and Akt phosphorylation along with the inhibition of intranuclear CHOP expression in human macrophages. CONCLUSIONS: These findings imply that controlling endoplasmic reticulum stress might provide new strategies for restoring reduced macrophage phagocytosis in sepsis-induced hyperglycaemia.

THE ACCUMULATION AND DISTRIBUTION OF VANADIUM, IRON, AND MANGANESE IN SOME SOLITARY ASCIDIANS.

The vanadium, iron, and manganese contents of 15 species of solitary ascidians belonging to the suborders Phlebobranchia and Stolidobranchia were determined by thermal neutron activation analysis. Vanadium was detectable in all species examined. In general, the vanadium content in various tissues of the Phlebobranchia was considerably higher than the iron and manganese contents. The blood cells especially contained a large amount of vanadium. The highest value (21 µg vanadium/mg dry weight) was obtained from blood corpuscles of Ascidia ahodori. Species in the suborder Stolidobranchia, on the other hand, had smaller quantities of vanadium in comparison with those in the suborder Phlebobranchia. The iron and manganese contents did not differ greatly between the two suborders. The data are considered in the light of physiological roles of these transition metals in ascidians.