title: The role of Kupffer cells in the hepatic response to silver nanoparticles.
abstract: Engineered nanoparticles are increasingly used in medical applications and day-to-day consumer products, leading to concerns about the potential environmental and human health impacts. Silver nanoparticles are particularly prevalent because of their use as anti-bacterial agents in many commonly available products. Nanoparticles (NPs) are believed to accumulate, often preferentially, in the liver. This study therefore investigates the effect of a silver NP (20 nm) on the liver, and in particular, the role of Kupffer cells (KCs; resident liver macrophages) in the overall inflammatory response in the organ. Cytokine expression in the normal liver was measured in terms of IL2, IL4, TNF-α, IFN-γ and IL10 released from the organ with significant up-regulation of TNF-α and IL10 being observed. For livers in which the KC population was specifically targeted and destroyed this cytokine increase was significantly decreased in comparison to the normal tissue. IL10 was secreted at approximately three times the concentration of TNF-α in all the test cases. The high levels of IL10 released from the normal tissue in comparison to the KC depleted livers suggest that the cytokine may help to protect against a pro-inflammatory response to these Ag NPs. This may indicate a potentially important role for KCs in the anti-inflammatory response and suggests that tolerance to the Ag NPs is favoured over a fully activated immune response. In addition, albumin production was measured as an indicator of hepatic function. It was noted that the liver function was unaffected by the Ag NPs.
authors.affiliation: Nanosafety Research Group, School of Life Sciences, Heriot-Watt University , Edinburgh , UK .
authors.forename: Ali
authors.initials: A
authors.lastname: Kermanizadeh
authors.forename: Caroline
authors.initials: C
authors.lastname: Chauché
authors.forename: Dominique
authors.initials: D
authors.lastname: Balharry
authors.forename: David M
authors.initials: DM
authors.lastname: Brown
authors.forename: Nilesh
authors.initials: N
authors.lastname: Kanase
authors.forename: Jorge
authors.initials: J
authors.lastname: Boczkowski
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanone
authors.forename: Vicki
authors.initials: V
authors.lastname: Stone
mesh_terms: D000818:Animals; D005260:Female; D007728:Kupffer Cells / Q000502:physiology*; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D012834:Silver / Q000737:chemistry*
chemical_list: D012834:Silver
keywords: Ag NPs; Kupffer cells; inflammatory response; liver; liver function