PMID- 32909489 OWN - NLM STAT- MEDLINE DCOM- 20201127 LR - 20210312 IS - 1743-5404 (Electronic) IS - 1743-5390 (Print) IS - 1743-5390 (Linking) VI - 14 IP - 8 DP - 2020 Oct TI - Evaluation of the skin-sensitizing potential of gold nanoparticles and the impact of established dermal sensitivity on the pulmonary immune response to various forms of gold. PG - 1096-1117 LID - 10.1080/17435390.2020.1808107 [doi] AB - Gold nanoparticles (AuNP) are largely biocompatible; however, many studies have demonstrated their potential to modulate various immune cell functions. The potential allergenicity of AuNP remains unclear despite the recognition of gold as a common contact allergen. In these studies, AuNP (29 nm) dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA). Soluble gold (III) chloride (AuCl(3)) caused lymph node (LN) expansion (SI 10.9), whereas bulk particles (Au, 942 nm) and AuNP did not. Next, the pulmonary immune effects of AuNP (10, 30, 90 microg) were assessed 1, 4, and 8 days post-aspiration. All markers of lung injury and inflammation remained unaltered, but a dose-responsive increase in LN size was observed. Finally, mice were dermally-sensitized to AuCl(3) then aspirated once, twice, or three times with Au or AuNP in doses normalized for mass or surface area (SA) to assess the impact of existing contact sensitivity to gold on lung immune responses. Sensitized animals exhibited enhanced responsivity to the metal, wherein subsequent immune alterations were largely conserved with respect to dose SA. The greatest increase in bronchoalveolar lavage (BAL) lymphocyte number was observed in the high dose group - simultaneous to preferential expansion of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP caused more modest elevations in BAL lymphocyte influx (predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T-cells and B-cells. Overall, these findings suggest that AuNP are unlikely to cause sensitization; however, established contact sensitivity to gold may increase immune responsivity following pulmonary AuNP exposure. FAU - Roach, K A AU - Roach KA AD - Allergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USA. FAU - Anderson, S E AU - Anderson SE AD - Allergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USA. FAU - Stefaniak, A B AU - Stefaniak AB AD - Respiratory Health Division (RHD), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USA. FAU - Shane, H L AU - Shane HL AD - Allergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USA. FAU - Boyce, G R AU - Boyce GR AD - Allergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USA. FAU - Roberts, J R AU - Roberts JR AD - Allergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USA. LA - eng GR - CC999999/ImCDC/Intramural CDC HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20200910 PL - England TA - Nanotoxicology JT - Nanotoxicology JID - 101233132 RN - 0 (Allergens) RN - 0 (Blood Proteins) RN - 0 (Cytokines) RN - 0 (Gold Compounds) RN - 11118-27-7 (gold chloride) RN - 7440-57-5 (Gold) SB - IM MH - Allergens/*toxicity MH - Animals MH - Blood Proteins/metabolism MH - Bronchoalveolar Lavage Fluid/cytology/immunology MH - Cytokines/metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Gold/*toxicity MH - Gold Compounds/*toxicity MH - Local Lymph Node Assay MH - Lung/*drug effects/immunology MH - Lymph Nodes/drug effects/immunology MH - Metal Nanoparticles/*toxicity MH - Mice MH - Mice, Inbred C57BL MH - Particle Size MH - Skin/*drug effects/immunology MH - Surface Properties PMC - PMC7945003 MID - NIHMS1672922 OTO - NOTNLM OT - Nanotoxicology OT - allergic contact dermatitis OT - allergic sensitization OT - gold nanoparticles OT - pulmonary immune response COIS- Disclosure statement No potential conflict of interest was reported by the author(s). EDAT- 2020/09/11 06:00 MHDA- 2020/11/28 06:00 PMCR- 2021/03/10 CRDT- 2020/09/10 08:41 PHST- 2020/09/11 06:00 [pubmed] PHST- 2020/11/28 06:00 [medline] PHST- 2020/09/10 08:41 [entrez] PHST- 2021/03/10 00:00 [pmc-release] AID - 10.1080/17435390.2020.1808107 [doi] PST - ppublish SO - Nanotoxicology. 2020 Oct;14(8):1096-1117. doi: 10.1080/17435390.2020.1808107. Epub 2020 Sep 10.