title: Serum enhanced cytokine responses of macrophages to silica and iron oxide particles and nanomaterials: a comparison of serum to lung lining fluid and albumin dispersions.
abstract: The potential hazard to humans exposed to nanomaterials such as silica and iron oxide was investigated using an in vitro macrophage cell culture system. Amorphous silica and iron oxide particles and nanomaterials (NMs) were dispersed in cell culture medium supplemented with either bovine serum albumin (BSA), lung lining fluid (LLF) or serum, in order to mimic the body fluids encountered during different routes of exposure in the body. End points investigated included macrophage viability and cytokine production. Silica NMs and particles (50 and 200 nm, respectively) were unmodified (plain) or aminated (NH2 ). Iron oxide NMs and particles, Fe3 O4 45 nm and Fe2 O3 280 nm were also used in this study. Silica particles and NMs induced a dose-dependent increase in cytotoxicity as measured by lactate dehydrogenase (LDH) release. Serum enhanced silica-induced interleukin (IL)-6, IL-10, IL-1β and MCP-1 release, whereas albumin partially inhibited MCP-1 release. Aminated silica, 50 nm was more potent than the 200-nm particles at inducing monocyte chemoattractant protein-1 (MCP-1) production when dispersed in medium or LLF, suggesting a size specific effect for these particles and this cytokine. Iron oxide particles were relatively inert compared with the silica particles and NMs; however, serum and albumin did affect cytokine release in some treatments. In conclusion, the data suggests that serum, compared with medium, BSA and LLF is very potent at enhancing macrophage responses to silica and iron oxide particles and NMs. Size was only influential in LLF for a limited number of parameters, whereas surface chemistry was not of consequence in this in vitro macrophage system.
authors.affiliation: School of Life sciences, Heriot-Watt University, Riccarton, Edinburgh, EH14 4AS, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Brown
authors.forename: Helinor
authors.initials: H
authors.lastname: Johnston
authors.forename: Eva
authors.initials: E
authors.lastname: Gubbins
authors.forename: Vicki
authors.initials: V
authors.lastname: Stone
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001826:Body Fluids / Q000737:chemistry; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000633:toxicity*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D000418:Albumins; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D005290:Ferric Compounds; D053583:Interleukin-1beta; D015850:Interleukin-6; D016753:Interleukin-10; C000499:ferric oxide; D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase
keywords: Cytokine; Dispersant; Iron oxide; J774; Nanomaterials; Silica