Copper Deficiency Suppresses Effector Activities of Differentiated U937 Cells

Abstract

Dietary copper (Cu) deficiency impairs both innate and acquired branches of immunity. Specific roles of Cu in the activation and effector activities of host-defense cells remain largely unknown. The effects of Cu status on effector activities of a monocytic cell line were investigated as an initial step in the elucidation of specific functions of Cu in phagocytic cells. Exposure of differentiating U937 human promonocytic cells to 5 mol/L 2,3,2-tetraamine (tet), a high affinity Cu chelator, for 4 d decreased cellular Cu by 62% without altering cellular Cu,Zn-superoxide dismutase (SOD) activity, Zn content, mitochondrial activity and protein synthesis. In contrast, Cu deficiency suppressed the respiratory burst activity and markedly compromised the ability of U937 cells to kill Salmonella. Similarly, treatment of RAW264.7 murine macrophages with 5 mol/L tet decreased cell Cu by 78% and Cu,Zn-SOD activity by 15% and increased bacterial survival by 180%. The tet-induced impairment of respiratory burst and bactericidal activities was blocked in cultures supplemented with Cu, but not Zn or Fe. In addition, lipopolysaccharide (LPS)-induced secretion of the inflammatory mediators, tumor necrosis factor-␣, interleukin (IL)-1␤, IL-6 and prostaglandin E 2 (PGE 2 ), was decreased by 30 -60% in tet-treated U937 cells. Flow cytometric analysis of the surface antigens CD11b and CD71 showed that the suppressed activities of Cu-deficient cells were not due to an attenuation in the degree of differentiation or secondary iron deficiency. These data demonstrate that U937 cells provide a useful model for examining the biochemical roles of Cu in monocyte activity. J. Nutr. 130: 1536Nutr. 130: -1542Nutr. 130: , 2000

Overexpression of Cellular Prion Protein Induces an Antioxidant Environment Altering T Cell Development in the Thymus

“…It is known that copper deprivation impairs both innate and adaptative immunity. For example, copper deficiency reduces the level of IL-2 mRNA and the secretion of this cytokine (30,53). Also, it has been clearly shown that murine PrP C might serve as a copper chelating or buffering agent in the outer side of the cell membrane (39,43).…”

Bacterial Copper Resistance and Virulence

“…The increase in Cu levels in this compartment may be related with the recruitment of ATP7A, as discussed above. Further support to this hypothesis comes from the observation that Cu deficiency suppresses respiratory burst, a bactericidal activity against Salmonella, and the secretion of the inflammatory mediators TNF-a, IL-1b, IL-6 and PGE2 in differentiating U937 human promonocytic cells [91]. In fact, the addition of the extracellular copper chelator BCS greatly enhanced S. typhimurium survival within bone marrow derived macrophages (BMM), and copper transport genes were dramatically up-regulated in BMM in response to either infection with S. typhimurium or treatment with LPS [92].…”

Evaluation of Il-6 Production by Human Blood Cells Incubated With Metal Complexes of Γ-Globulin

“…Несмотря на извест-ную роль катионов железа [9], цинка [16, 18] и меди [10] в выработке IL-6, индукция цитокина в организме поддерживается на уровне определен-ной стабильности и не связана напрямую с про-цессами транспорта и обмена в микроокружении клетки катионов металлов. Так, хелатирование цинка или железа не приводит к снижению инду-цированной секреции IL-6 [10], на выработку ко-торого не влияет и пищевой дефицит цинка [12]. Одновременно, действуя через рецепторы систе-мы врожденного иммунитета (TLR), связанные с активацией ассоциированной с рецептором IL-1 киназы (IRAK), катионы цинка снижают ин-дуцирующие эффекты в отношении выработки IL-6 [17].…”

“…Поскольку в развитии воспаления и индуктив-ной фазы иммунного реагирования, вследствие общности внутриклеточных путей трансдукции сигнала, выработка IL-1β индуцируется одновре-менно и регулируется сонаправленно продукции IL-6 [10,13,17], изменения выработки IL-1β и IL-6 в условиях меняющейся антигенной или ме-таболической нагрузки, как правило, происходят параллельно и взаимосвязанно [16,18], а IL-1β выступает фактором, индуцирующим продукцию IL-6 [8,11,15], обоснованно полагать, что метал-локомплексы белков γ-глобулиновой фракции могут вовлекаться в регуляцию выработки IL-6, рассматривающегося в качестве основного ци-токина, усиливающего экспрессию генов острой фазы воспаления [11].…”