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Applications of Biotechnology: Biology Doing Chemistry
Published in Richard J. Sundberg, The Chemical Century, 2017
The related granulyte macrophage colony-stimulating factor (GM-CSF) stimulates formation of neutrophils, macrophages, and eosinophils by bone marrow. It is a 127 AA polypeptide. Three forms of recombinant GM-CSF have been developed including Molgramostim (produced in E. coli), Regramostim (produced in Chinese hamster ovary cells) and Sargramostim (produced in yeast). The latter also has a leucine substitution at position 23. In addition to indications similar to G-CSF, GM-CSF was originally approved to accelerate myeloid recovery in patients after bone marrow transplants. There is some evidence that GM-CSF stimulates the immune response toward tumor cells. The benefits of treatment with G-CSF and GM-CSF include reduced risk of infection, increased likelihood of completion of the entire chemotherapy course, and, in some cases, more frequent chemotherapeutic treatments. There is only very limited data that the use of G-CSF has favorable long-term outcome, and it is currently recommended only for patients at significant (>20%) risk for infection.
Polymers for Artificial Joints
Published in Severian Dumitriu, Valentin Popa, Polymeric Biomaterials, 2020
Masayuki Kyomoto, Toru Moro, Kazuhiko Ishihara
The contribution of the cells present within the macrophage-rich inflammatory tissue to the induction of bone resorption and implant loosening involves multiple cellular mechanisms. The macrophages are activated by the particles and subsequently release proinflammatory cytokines and other agents that induce bone resorption. Macrophage products capable of inducing bone resorption include interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, arachidonic acid metabolites, and degradative enzymes. The existence of multiple factors at one site is likely to accelerate bone destruction. IL-1α, IL-1β, and TNF-α may also induce secondary effects on other cell types (such as osteoblasts) in the interfacial membrane, resulting in the release of matrix-degrading enzymes, including collagenase, stromelysin, gelatinases, and plasminogen activators. Granulocyte/macrophage colony-stimulating factor (GM-CSF) has also been implicated in cellular proliferation in the interfacial membrane around implants. Other cytokines that may exhibit immunomodulatory roles include IL-12, which is increased in the pseudosynovial fluid in patients with aseptic loosening of hip joint replacement. A primary response of macrophages to particulate debris is the increased release of TNF-α. TNF-α release results in part from the exposure of macrophages to particles, which activates the transcription factor NF-κB; this reaction is related to membrane receptor events. Alteration of the bone surface by these proteases may stimulate osteoclast bone-resorbing activity and may influence the recruitment and adhesion of mononuclear phagocyte osteoclast precursors at the bone–implant interface.
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.
Pro-inflammatory responses induced by A. fumigatus and A. versicolor in various human macrophage models
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Elisabeth Øya, Anita Solhaug, Anette K. Bølling, Reidun Øvstebø, Tonje B. Steensen, Anani K.J. Afanou, Jørn A. Holme
Elutriation-purified, cryopreserved human primary monocytes (>90% purity) (Lund et al. 2000) from consenting, healthy donors were thawed and re-suspended in RPMI 1640 supplemented with 10% heat-inactivated FBS and penicillin (100 U/mL)/streptomycin (100 μg/mL). Cells were seeded at a density of 1.5 × 105 cells/cm2 and incubated in a humidified atmosphere at 37°C under 5% CO2. The monocytes were cultivated for 24 h to enable adhering to the plastic and nonadherent peripheral blood mononuclear cells (PBMCs) were gently washed off. MDMs were then differentiated in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF, 50 ng/mL) for 7 d (Solhaug et al. 2015). The medium was refreshed on day 4 and on the day of exposure. Macrophage differentiation was verified by flow cytometric analysis of CD14, CD71, CD11b, and CD206 as described below. Cells were approximately 70% confluent on the day of treatment. Upon exposure, cells were incubated with mold particles at indicated concentrations (1 ng/mL-50 µg/mL) for 6 or 24 h. When the TLR2 and TLR4 antagonists were utilized, these compounds were added to the cells 1 h prior to mold exposures. Cells from different donors were used for the biological replicates of the experiments.
Evaluation of the proinflammatory effects of contaminated bathing water
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Anas A. Sattar, Wondwossen Abate, Gyorgy Fejer, Graham Bradley, Simon K. Jackson
Key immune cells involved in inflammation, monocytes, and macrophages are highly responsive cell types for LPS signaling both in vivo and in vitro (Fejer et al. 2013; Liu et al. 2011). MPI cells are newly described self-renewing, granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent, non-transformed macrophages. In the presence of GM-CSF, the MPI cells are differentiated into macrophages and the phenotype of these macrophages resembles alveolar macrophages (AM) as reported by Fejer et al. (2013). GM-CSF-treated MPI cells release a range of cytokines and the cytokines selected in the present investigation were chosen for their relevance in lung inflammation.