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.

Carbon Nanoparticles Inhibit the Antimicrobial Activities of the Human Cathelicidin LL-37 through Structural Alteration

“…These proteins can include, but are not limited to, albumin, surfactant proteins A and D, and IgG (33)(34)(35). This is also consistent with recent studies that revealed that diesel exhaust nanoparticles have the capacity to bind to a wide range of proteins that are commonly found in bronchoalveolar lavage fluid, and that this process subsequently increased diesel exhaust particle and carbon nanoparticle uptake into the differentiated macrophage-like cell line THP-1 (36). However, characterization of any functional alteration of the proteins analyzed remains to be undertaken.…”

Protein corona: implications for nanoparticle interactions with pulmonary cells

“…Once internalized in AMs, NPs are slowly cleared from the lungs by particle dissolution and cell migration. The rate at which AMs phagocytize NPs can be influenced significantly by the composition of the corona [ 17 ]. Coating magnetite and TiO 2 with SP-A increases their uptake in macrophages suggesting that the NP protein corona can affect particle recognition, phagocytosis, and processing by AMs [ 32 ].…”

“…It was found that anionic nanoparticles selectively adsorbed SP-B 1–25 , but not SP-C. Recent studies showed that inhaled diesel exhaust NPs exhibit a corona of SP-A, SP-D, and albumin [ 17 ]. The role of albumin in the translocation of intravenously injected gold NPs (AuNPs) to different organs has been described [ 18 ].…”

Structure and Function of Adsorbed Hemoglobin on Silica Nanoparticles: Relationship between the Adsorption Process and the Oxygen Binding Properties

“…Indeed, the adsorption of biomolecules on the surface of NMs in the biological medium leads to the formation of a complex and dynamic corona, giving NMs their 'biological identity' 27,28 . The protein corona determines the NM uptake and its biological outcome [29][30][31] . Moreover, the control of the conformation and the activity of the adsorbed proteins is necessary to achieve good material biocompatibility 32,33 .…”