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Two-Dimensional Nanomaterials for Drug Delivery in Regenerative Medicine
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Zahra Mohammadpour, Seyed Morteza Naghib
Graphene has also been used as a vaccine delivery platform to activate antigen-presenting dendritic cells (DCs). Sinha et al. functionalised graphene with dextran and used it as an ovalbumin carrier to activate cytotoxic T cells (Sinha et al. 2017). Increased colloidal stability and cell internalisation of the nanocomposite was ascribed to the dextran. At the same time, the high loading of ovalbumin on the surface of the nanocomposite was related to the large specific surface area of GO and its hydrophobic basal plane. Based on the in vivo experiments, they observed that the production of cytotoxic T cells was induced by ovalbumin-loaded graphene nanocomposite, which subsequently resulted in the prevention of tumour growth. Therefore, they proposed the delivery system potentially as a cancer vaccine. The same research group also developed a 3D alginate scaffold into which graphene was embedded (Sinha et al. 2019). They loaded it with ovalbumin, granulocyte-macrophage colony-stimulating factor, and CpG. They offered the system to be promising in cancer vaccination.
Endotoxin
Published in Harriet A. Burge, Bioaerosols, 2020
In contrast to its deleterious effects on lung function, endotoxin’s ability to stimulate the immune system (i.e., its adjuvant properties) can have beneficial effects. The adjuvant effects of endotoxin are primarily due to specific binding of lipid A. Binding of lipid A to a cell surface receptor on macrophages results in production and secretion of a variety of important cytokines and arachidonic acid metabolites. Tumor necrosis factor (TNFa), the cytokine most closely associated with the toxic effects of endotoxin, is produced in large quantities by macrophages stimulated with picogram per milliliter quantities of endotoxin. However, a number of other cytokines, including interferons, and granulocyte-macrophage colony-stimulating factor, are also produced. These cytokines play important roles in regulating T-cell as well as phagocytic function. Lipid A has been shown to reverse T-cell tolerance to polysaccharide antigens, a property that is being exploited in the design of new antimalarial vaccines (Baker et al., 1992; Richards et al., 1989). Unfortunately, the adjuvant properties of endotoxin may also play a role in allergic sensitization, as suggested by at least one recent study (Rose et al., 1993).
Biocompatibility of Powdered Materials: The Influence of Surface Characteristics
Published in Michel Nardin, Eugène Papirer, Powders and Fibers, 2006
Patrick Frayssinet, Patrice Laquerriere
The macrophage is a cell able to internalize the particles by phagocytosis in special internal compartments in order to destroy them by physico-chemical mechanisms (Figure 12.2 and Figure 12.3). Phagocytosis is the ingestion of large particles, minerals, microorganisms, or dead cells in large vesicles called phagosomes. These cells can also fuse to form multinucleated giant cells. Interleukin-4 (IL-4) is able to induce foreign body giant cells from human monocytes and macrophages.2 This effect is optimized with granulocyte macrophage–colony stimulating factor (GM–CSF) or IL-3 (Interleukin-3), dependent on the concentration of IL-4.
Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Sreejesh Sreedharan, Georgios Zouganelis, Samantha J Drake, Gyanendra Tripathi, Ali Kermanizadeh
In another study, healthy and OVA sensitized 7-week-old male ICR mice were exposed to MWCNT (approximately 65 nm; surface area, 26 m2/g; carbon purity, 99.8%; fiber length not specified) once a week for a total of 6 weeks via intratracheal instillation where each NM dose was 50 μg/animal (Inoue et al. 2009). Concurrently, OVA-sensitized T-cells isolated from the spleens of allergic mice were exposed to MWCNTs at concentration range of 0.1–1 μg/ml as well as 10 ng/ml recombinant mouse granulocyte macrophage-colony stimulating factor. The results showed aggravated inflammation in the lungs of diseased animals compared to control mice as evidenced by increased BALF total cell, neutrophil, and eosinophil numbers. Further, histological analysis demonstrated that in combined treatment with OVA and NMs increasing numbers of neutrophils and eosinophils was detected accompanied by lymphocyte sequestration into the lung parenchyma. Similarly, MWCNT exposure in asthmatic animals resulted in an elevated number of goblet cells in the bronchial epithelium which was not observed in the other treatment groups. The MWCNT and OVA exposure also amplified lung protein levels of inflammatory cytokines and chemokines, namely, IL4, IL5, IL13, IL18, IL33, and IFN-Ƴ. Finally, the in vitro exposure of MWCNT significantly enhanced allergen-specific syngeneic T-cell proliferation. Data from this study suggest that MWCNTs might potentially intensify allergic airway inflammation (Inoue et al. 2009).
A comprehensive summary of disease variants implicated in metal allergy
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Pulmonary alveolar proteinosis (PAP) is a relatively uncommon lung disease characterized by the accumulation of surfactant lipids and proteins within the alveolar space (Wang et al. 2012). Impaired clearance mechanisms are responsible for the buildup of these acellular components, which impair gas exchange, and eventually produce respiratory failure and death. Several different sources of PAP have been identified, and three corresponding variants of the disease were described to reflect these different origins of disease. Congenital PAP results from genetic mutations in innate immune cell receptors, autoimmune PAP involves adaptive immune-mediated interference with normal pulmonary clearance mechanisms, and secondary PAP emerges as a complication of infections, malignancies, or toxic exposures (Ben-Dov and Segel 2014; Santos et al. 2020). Accordingly, PAP is known to occur in both worker populations and the general public. The cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) plays a central role in the pathogenesis of all three variants of PAP, as it mediates the terminal differentiation of alveolar macrophages, which are responsible for catabolizing the offending molecules and clearing them from the lower airways (Trapnell et al. 2019). Accordingly, disease onset corresponds with the introduction of disruptions in GM-CSF signaling and alveolar macrophage functionality.
Traffic-related particulate matter aggravates ocular allergic inflammation by mediating dendritic cell maturation
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Moonwon Hwang, Sehyun Han, Jeong-Won Seo, Ki-Joon Jeon, Hyun Soo Lee
This procedure was previously described by Lee et al. (2015). The femurs of naıve BALB/c mice were removed and irrigated with a syringe to collect bone marrow dendritic cells (BMDC). The bone marrow cells were washed and plated (1 × 105/ml) in RPMI 1640 medium with 20 ng/ml mouse granulocyte-macrophage colony-stimulating factor (BioLegend), 10% fetal bovine serum, and 1% penicillin/streptomycin. The loosely adherent cells were collected on day 7. To stimulate T cells in vitro, ipsilateral cervical lymph nodes (LNs) were harvested after the topical challenge. T cells were enriched with magnetic-activated cell sorting using anti-CD90.2 antibodies (Miltenyi Biotec, Germany) and then T cells were counted via a trypan blue exclusion assay and plated in round-bottom 96-well plates at a concentration of 1 × 106/ml. The immature BMDCs as described above were plated with OVA at a concentration of 0.5 × 106/ml with T cells. All culture wells were plated in triplicate for up to 72 hr.