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Immune Modulation In Sepsis
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Janet M. J. Hammond, Peter D. Potgieter
Historically endotoxin was the first mediator of the inflammatory cascade to be identified. During the 1960s, the structural features of gram-negative bacterial lipopolysaccharide were identified: an inner core sugar region, a common toxic lipid A moiety, and an antigenically distinct O polysaccharide side chain. Experimental studies suggested that antibodies directed to epitopes in the inner-core sugar region of the lipopolysaccharide (which are widely shared by gram-negative bacilli) may be protective [130–132].
Endotoxin Detection in Body Fluids: Chemical Versus Bioassay Methodology
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
The first practical assay for endotoxin (as “pyrogen”) was a rabbit bioassay based on the work of Seibert (1). Over a period spanning her entire research career, Florence Seibert elucidated the cause of “injection” and “protein” fevers, proposed methods to produce nonpyrogenic intravenous solutions, suggested a standard “pyrogen,” and provided a model for the first compendial test for pyrogen (2–5). The current compendial pyrogen test consists of injecting a solution into the marginal ear vein of a rabbit under standardized conditions and measuring its rectal temperature over a period of time (6). The pyrogen test has been used with only slight changes since it was first described in Volume XII of the Pharmacopoeia of the United States of America in 1942 (7). Because the chemical nature of pyrogen as endotoxin was only beginning to be elucidated by the time the pyrogen test was published, no alternative (i.e., chemical) test could even be considered. The early purification work of Boivin et al. (8) and Westphal et al. (9) paved the way for characterization of the lipopolysaccharide component of endotoxin to the point where several unique components were identified. Two of these in particular, 2-keto-3-deoxy-octonic acid (or 3-deoxy-D-manno-2-octulosonic acid, KDO) and β-OH fatty acids, could be used as a chemical test for endotoxin (10,11).
Acquired Immunity
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
An antigen is a substance capable of stimulating the immune system of the host to produce a specific response to it. Most antigens are proteins, polysaccharide or lipid macromolecules, but often the antigenic properties are determined by their carbohydrate moieties. Lipopolysaccharides in bacterial cell walls are important antigens. N-acetylglucosamine is the antigenic determinant of the cell wall of Streptococcus A, whereas N-acetylgalactosamine is the main determinant for Streptococcus C.
Macrophage membrane biomimetic drug delivery system: for inflammation targeted therapy
Published in Journal of Drug Targeting, 2023
Yulu Zhang, Yu Long, Jinyan Wan, Songyu Liu, Ai Shi, Dan Li, Shuang Yu, Xiaoqiu Li, Jing Wen, Jie Deng, Yin Ma, Nan Li
Bacterial infections are the most common type of infectious disease and can affect a wide range of organs and tissues, even causing sepsis and septic shock, and have serious public health consequences [98,99]. Endotoxin, also known as lipopolysaccharide (LPS), is an important pathogenic trigger for Gram-negative bacterial sepsis. It can reach target organs after circulation and cause lethal damage to the organism [100,101]. Effective removal of LPS is an important method for the successful treatment of bacterial infections and their complications. Macrophages are cells that can respond rapidly to microenvironmental signals. During bacterial infection, macrophages are among the first responders. Macrophages recognise pathogen-associated molecular patterns (PAMPs), such as LPS, through toll-like pattern recognition receptors on them [102]. LPS binding to macrophages activates TLR4 and activates transcription factors (e.g. interferon regulatory factors) and NF-κB to initiate inflammatory responses as a means of regulating bacterial phagocytic uptake and intracellular transport [103]. Therefore, the critical role played by macrophages and their surface receptors in LPS signalling provides new ideas for the treatment of bacterial infections and their complications.
Deer antler based active ingredients have protective effects on LPS/d -GalN-induced acute liver injury in mice through MAPK and NF-κB signalling pathways
Published in Pharmaceutical Biology, 2022
Guixiang He, Quanmin Zhao, Yan Zhao, Ying Zong, Shigang Gu, Mengjie Li, Renjie Li, Jiaxin Sun
Macrophages are the most important immune cells and play a variety of immunomodulatory roles in various inflammatory diseases. Once activated, macrophages release a series of inflammatory cytokines (Fujiwara and Kobayashi 2005). Lipopolysaccharide is a cell wall component of Gram-negative bacteria, which interferes with the receptors of immune cells (Chen et al. 2018). Lipopolysaccharide is one of the most potent activators of mononuclear macrophages and is known to produce pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α and pro-inflammatory mediators, such as NO and PGE2 (Yang et al. 2012; Abarikwu 2014). Therefore, we selected mouse monocyte macrophages RAW 264.7 to screen the isolated and purified antler base protein extract, and found that the NO production of RAW264.7 cells after 4 h pre-treatment with R1 protein component was significantly reduced. We also measured the cytokines IL-6, IL-1β and TNF-α to further verify the anti-inflammatory effect of the R1 protein component. The results demonstrated that pre-treatment with R1 protein component, inflammatory factors were reduced in a dose-dependent manner. Therefore, we speculate that the R1 protein component of deer antler base may have a pre-protective effect on ALI through anti-inflammatory effects.
Structure-guided approach on the role of substitution on amide-linked bipyrazoles and its effect on their anti-inflammatory activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Souraya A. Domiati, Khaled H. Abd El Galil, Mohammed A. S. Abourehab, Tamer M. Ibrahim, Hanan M. Ragab
COX enzymes exist in several distinct isoforms; the most important of which in inflammation are COX-1 and COX-210,12. The constitutive COX-1 is responsible for cytoprotection of the gastrointestinal (GI) tract together with controlling renal function, while the inducible COX-2 is upregulated by pro-inflammatory mediators such as endotoxins, mitogens, or cytokines, and is thus considered a major cause of inflammatory conditions13. Despite the important effects of cytokines in the activity of many cells, they are highly implicated in the development of inflammation as a result of bacterial infection and/or exposure to lipopolysaccharides (LPS)14–17. The production of proinflammatory cytokines, not only results in upregulation of COX-2, but also leads to the release of interleukin (IL)-1β, IL-8, tumour necrosis factor-alpha (TNF-α), IL-6, and IL-12 which are highly implicated in inflammation.