title: Fibrillar vs crystalline nanocellulose pulmonary epithelial cell responses: Cytotoxicity or inflammation?
abstract: Nanocellulose (NC) is emerging as a highly promising nanomaterial for a wide range of applications. Moreover, many types of NC are produced, each exhibiting a slightly different shape, size, and chemistry. The main objective of this study was to compare cytotoxic effects of cellulose nanocrystals (CNC) and nanofibrillated cellulose (NCF). The human lung epithelial cells (A549) were exposed for 24 h and 72 h to five different NC particles to determine how variations in properties contribute to cellular outcomes, including cytotoxicity, oxidative stress, and cytokine secretion. Our results showed that NCF were more toxic compared to CNC particles with respect to cytotoxicity and oxidative stress responses. However, exposure to CNC caused an inflammatory response with significantly elevated inflammatory cytokines/chemokines compared to NCF. Interestingly, cellulose staining indicated that CNC particles, but not NCF, were taken up by the cells. Furthermore, clustering analysis of the inflammatory cytokines revealed a similarity of NCF to the carbon nanofibers response and CNC to the chitin, a known immune modulator and innate cell activator. Taken together, the present study has revealed distinct differences between fibrillar and crystalline nanocellulose and demonstrated that physicochemical properties of NC are critical in determining their toxicity.
authors.affiliation: Exposure Assessment Branch/NIOSH/CDC, Morgantown, WV, USA.
authors.forename: Autumn L
authors.initials: AL
authors.lastname: Menas
authors.affiliation: Exposure Assessment Branch/NIOSH/CDC, Morgantown, WV, USA.
authors.forename: Naveena
authors.initials: N
authors.lastname: Yanamala
authors.affiliation: Exposure Assessment Branch/NIOSH/CDC, Morgantown, WV, USA.
authors.forename: Mariana T
authors.initials: MT
authors.lastname: Farcas
authors.affiliation: Institute of Public Health, Section of Occupational Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Russo
authors.affiliation: Pathology & Physiology Research Branch/NIOSH/CDC, Morgantown, WV, USA.
authors.forename: Sherri
authors.initials: S
authors.lastname: Friend
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Fournier
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Star
authors.affiliation: Department of Public Health, Division of Occupational Medicine, University of Naples Federico II, Naples, Italy.
authors.forename: Ivo
authors.initials: I
authors.lastname: Iavicoli
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Shurin
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Ulla B
authors.initials: UB
authors.lastname: Vogel
authors.affiliation: Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
authors.affiliation: Health Effects Laboratory Division/NIOSH/CDC, Morgantown, WV, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Beezhold
authors.affiliation: Exposure Assessment Branch/NIOSH/CDC, Morgantown, WV, USA.
authors.forename: Elena R
authors.initials: ER
authors.lastname: Kisin
authors.affiliation: Exposure Assessment Branch/NIOSH/CDC, Morgantown, WV, USA; Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA. Electronic address: ats1@cdc.gov.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
mesh_terms: D000072283:A549 Cells; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000166:cytology; D057139:Nanofibers / Q000633:toxicity*; D053758:Nanoparticles / Q000633:toxicity*
chemical_list: D016207:Cytokines; D002482:Cellulose
keywords: Cytokine production; Cytoxicity; Lung epithelial cells; Nanocellulose; Oxidative stress