title: Protein corona formation in bronchoalveolar fluid enhances diesel exhaust nanoparticle uptake and pro-inflammatory responses in macrophages.
abstract: In biological fluids nanoparticles bind a range of molecules, particularly proteins, on their surface. The resulting protein corona influences biological activity and fate of nanoparticle in vivo. Corona composition is often determined by the biological milieu encountered at the entry portal into the body, and, can therefore, depend on the route of exposure to the nanoparticle. For environmental nanoparticles where exposure is by inhalation, this will be lung lining fluid. This study examined plasma and bronchoalveolar fluid (BALF) protein binding to engineered and environmental nanoparticles. We hypothesized that protein corona on nanoparticles would influence nanoparticle uptake and subsequent pro-inflammatory biological response in macrophages. All nanoparticles bound plasma and BALF proteins, but the profile of bound proteins varied between nanoparticles. Focusing on diesel exhaust nanoparticles (DENP), we identified proteins bound from plasma to include fibrinogen, and those bound from BALF to include albumin and surfactant proteins A and D. The presence on DENP of a plasma-derived corona or one of purified fibrinogen failed to evoke an inflammatory response in macrophages. However, coronae formed in BALF increased DENP uptake into macrophages two fold, and increased nanoparticulate carbon black (NanoCB) uptake fivefold. Furthermore, a BALF-derived corona increased IL-8 release from macrophages in response to DENP from 1720 ± 850 pg/mL to 5560 ± 1380 pg/mL (p = 0.014). These results demonstrate that the unique protein corona formed on nanoparticles plays an important role in determining biological reactivity and fate of nanoparticle in vivo. Importantly, these findings have implications for the mechanism of detrimental properties of environmental nanoparticles since the principle route of exposure to such particles is via the lung.
authors.affiliation: a BHF/University of Edinburgh Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK ;
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Shaw
authors.affiliation: b Laboratory for Molecular and Cellular Pharmacology , School of Biomedical Sciences, University of Queensland , Brisbane , Australia ;
authors.forename: Gysell M
authors.initials: GM
authors.lastname: Mortimer
authors.affiliation: b Laboratory for Molecular and Cellular Pharmacology , School of Biomedical Sciences, University of Queensland , Brisbane , Australia ;
authors.forename: Zhou J
authors.initials: ZJ
authors.lastname: Deng
authors.affiliation: a BHF/University of Edinburgh Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK ;
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Carter
authors.affiliation: a BHF/University of Edinburgh Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK ;
authors.forename: Shea P
authors.initials: SP
authors.lastname: Connell
authors.affiliation: a BHF/University of Edinburgh Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK ;
authors.forename: Mark R
authors.initials: MR
authors.lastname: Miller
authors.affiliation: c MRC/University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK.
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.affiliation: a BHF/University of Edinburgh Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK ;
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: a BHF/University of Edinburgh Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK ;
authors.forename: Patrick W F
authors.initials: PW
authors.lastname: Hadoke
authors.affiliation: b Laboratory for Molecular and Cellular Pharmacology , School of Biomedical Sciences, University of Queensland , Brisbane , Australia ;
authors.forename: Rodney F
authors.initials: RF
authors.lastname: Minchin
mesh_terms: D001798:Blood Proteins / Q000737:chemistry; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002460:Cell Line; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011485:Protein Binding; D000066970:Protein Corona / Q000378:metabolism*; D013499:Surface Properties; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D001798:Blood Proteins; D016209:Interleukin-8; D000066970:Protein Corona; D001335:Vehicle Emissions
keywords: BALF; cardiovascular disease; diesel exhaust particles; inflammation; nanoparticles; nanotoxicology; particle uptake; protein corona