NiO and Co3O4 nanoparticles induce lung DTH-like responses and alveolar lipoproteinosis

Abstract

Lung exposure to metal oxide nanoparticles (NPs) comprising soluble metal haptens may produce T-helper cell type 1 (Th1)-and Th17-associated delayed-type hypersensitivity (DTH) responses and pulmonary alveolar proteinosis (PAP).In order to study this, haptenic metal oxide NPs (NiO, Co 3 O 4 , Cr 2 O 3 and CuO) were instilled into the lungs of female Wistar rats, and the immunoinflammatory responses were assessed at 24 h and 4 weeks post-instillation. Primary culture of alveolar macrophages from Wistar rats was used to evaluate the effect of the NPs on the ability to clear surfactant.NiO NPs induced chronic interstitial inflammation and pro-inflammatory Th1 and Th17 immune responses characterised by increases in the cytokines monocyte chemotactic protein (MCP)-1/ CCL2, interleukin (IL)-12 p40, interferon-c and IL-17A, whilst similar pathological responses induced by Co 3 O 4 NPs were associated with increases in MCP-1/CCL2 and IL-12 p40. However, neither Cr 2 O 3 nor CuO NPs elicited immunoinflammatory reactions. PAP was induced by both NiO and Co 3 O 4 NPs during the chronic phase. PAP was associated with over-production of surfactant by proliferation of type II cells and impaired clearance of surfactant by macrophages.These findings have implications for the risk management of occupational NP exposure and provide evidence that haptenic metal oxide NPs can induce chronic progressive lung immune responses via a DTH-like mechanism.

Adjuvanticity and Toxicity of Cobalt Oxide Nanoparticles as An Alternative Vaccine Adjuvant

“…n Rationale for dose selection Based on our previous study, we selected the dose of I-Alum as 2.0 mg per mouse [17]. In contrast, the dose of Co 3 O 4 NPs was selected as 25 µg per mouse based on the inflammogenicity in the lung; instillation of 419 µg/rat of Co 3 O 4 NPs showed acute neutrophilic inflammation and chronic lymphocytic/neutrophilic inflammation with alveolar lipoproteinosis [19]. n Cytotoxicity assay Mouse macrophage cell line, RAW264.7, was cultured at 37°C with 5% CO 2 in DMEM with l-glutamine, antibiotics (penicillin and streptomycin) and 10% heat-inactivated fetal bovine serum.…”

“…The levels of endotoxin in the particle suspensions were measured using a Limulus Amebocyte Lysate assay (Cambrex, MD, USA). The solubility of Co 3 O 4 NPs and I-Alum was tested in the acidic artificial lysosomal fluid (pH 5.5) or basic artificial interstitial fluid (pH 7.4) according the previously described method [19]. n Rationale for dose selection Based on our previous study, we selected the dose of I-Alum as 2.0 mg per mouse [17].…”

“…As so very few adjuvants are capable of eliciting a Th1 response it was considered that one of these NPs could be utilized to improve Th1 immunity against a model antigen, ovalbumin (OVA). In this study, we selected Co 3 O 4 NPs as a candidate adjuvant because Co 3 O 4 NPs produced a Th1 response without the severe delayed-type hypersensitivity pathology seen with NiONPs [19]. The aim of this study was to determine whether Co 3 O 4 NPs could be suitable for use as an adjuvant by inducing a balanced Th1 and Th2 response to the model antigen OVA, given subcutaneously to female C57BL/6 mice.…”

“…In our previous work, we found both nickel oxide NPs (NiONPs) and cobalt oxide NPs (Co 3 O 4 NPs) were capable of inducing a Th1 response in the lungs of female Wistar rats [19]. As so very few adjuvants are capable of eliciting a Th1 response it was considered that one of these NPs could be utilized to improve Th1 immunity against a model antigen, ovalbumin (OVA).…”

Immune System and Environmental Xenobiotics - The Effect of Selected Mineral Fibers and Particles on the Immune Response

“…Other airborne and engineered nanoparticles in addition to nickel, such as carbon nanotubes (He et al, 2011), titanium dioxide , cobalt -Co 3 O 4 (Cho et al, 2011a) or quantum dots (Jacobsen et al, 2009) has been reported to induce lung inflammation. Anoher example is ZnO nanoparticles (ZnO NP) discovered to induce eosinophilia, proliferation of airway epithelial cells, goblet cell hyperplasia, and pulmonary fibrosis.…”