IgE-mediated (immediate) hypersensitivity
Gabriel Virella in Medical Immunology, 2019
Role of eosinophils in the late phase. Eosinophils are attracted to the site where an immediate hypersensitivity reaction is taking place by chemotactic factors released by basophils, mast cells, and Th2 lymphocytes, including the following: ECF-A and PAF, preformed chemotactic factors released during basophil or mast cell degranulation.Leukotriene B4, synthesized and released by stimulated basophils/mast cells.Interleukin-5, released by activated Th2 lymphocytes, mast cells, and eosinophils.
Imaging of Cardiovascular Disease
George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos in Handbook of Small Animal Imaging, 2018
Active inflammatory cells produce a leukotriene B4 (LTB4) and secrete it as a potent chemotactic agent. In leukocytes, the leukotriene induces the adhesion and activation of the cells on the endothelium, while in neutrophils, LTB4 induces the formation of reactive oxygen species and the release of lysosome enzymes by these cells, contributing to the progression of inflammatory processes. Recently, a radiolabeled LTB4 receptor antagonist, 99mTc-RP517, has been developed for in vivo imaging of acute inflammation or infection. The tracer 99mTc-RP517 has a unique ability to label white blood cells in vivo after intravenous injection and has been noted to selectively localize to areas of inflammation (Serhan and Prescott 2000).
Osteoarthritis
Nicole M. Farmer, Andres Victor Ardisson Korat in Cooking for Health and Disease Prevention, 2022
In assessing the value of omega 6 and omega 3 to inflammation, it is important to highlight that both omega 6 and omega 3 are metabolically and functionally distinct and often have important opposing physiological effects. For instance, ingestion of EPA and DHA leads to displacement of AA from cellular membranes (Simopoulos, 2016). It also leads to (1) decreased production of prostaglandin E2 metabolites; (2) decreased concentrations of thromboxane A2, a potent platelet aggregator and vasoconstrictor; (3) decreased formation of leukotriene B4, an inducer of inflammation and a powerful inducer of leukocyte chemotaxis and adherence; (4) increased concentrations of thromboxane A3, a weak platelet aggregator and vasoconstrictor; (5) increased concentrations of prostacyclin PGI3, leading to an overall increase in total prostacyclin by increasing PGI3 without decreasing PGI2 (both PGI2 and PGI3 are active vasodilators and inhibitors of platelet aggregation); and (6) increased concentrations of leukotriene B5, a weak inducer of inflammation and chemotactic agent (Simopoulos, 2016). With regard to OA, the omega 3 essential fatty acids may therefore be involved in altering inflammatory response in chondrocytes through inhibiting IL-1-induced MMP3, MMP13, ADAMTS4, and ADAMTS5.
Investigational drugs in phase II clinical trials for acute coronary syndromes
Published in Expert Opinion on Investigational Drugs, 2020
Amit Rout, Ajaypaul Sukhi, Rahul Chaudhary, Kevin P Bliden, Udaya S Tantry, Paul A Gurbel
Leukotrienes are mainly derived from arachidonic acid via the 5- lipoxygenase (5-LO) pathway in leukocytes. 5-LO, along with 5-lipooxygenase activating protein (FLAP), initially leads to the formation of precursor leukotriene A4. Leukotriene B4 (LTB4) is a potent leukocyte activator and chemokine. The cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are potent vasoactive and inflammatory mediators [5,6]. Coronary artery disease (CAD) is an atheroinflammatory condition involving endothelial dysfunction, infiltration of inflammatory cells, and platelets into the arterial vessel wall, smooth muscle proliferation, and atherogenesis. 5-LO pathway mediators and products are increasingly expressed in the unstable atherosclerotic lesions and play a significant role in inflammation and progression of CAD and ACS [5,6].
Pinellia ternata attenuates carotid artery intimal hyperplasia and increases endothelial progenitor cell activity via the PI3K/Akt signalling pathway in wire-injured rats
Published in Pharmaceutical Biology, 2020
Hai-Ke Lu, Yan Huang, Xiao-Yu Liang, Ying-Yi Dai, Xin-Tong Liu
The pathogenesis of intimal hyperplasia after vascular injury is thought to involve different signalling cascades that eventually converge on vascular smooth muscle cells (VSMCs), stimulating their proliferation and migration and enhancing the secretion of extracellular matrix (Asahara et al. 1999). Bäck et al. (2005) reported that inhibition of leukotriene B4 and the signalling of its receptor reduces intimal hyperplasia during the response to vascular injury. In vascular ECs, tangerine peels and PT tubers may exert therapeutic effects in the treatment of carotid atherosclerosis by upregulating the expression of PBK and p-Akt (Chen et al. 2014). Guo et al. (2017) found that Gualou Xiebai Banxia decoction plays a role in atherosclerotic Apo-E–/– mouse lesions, and the mechanism may be related to the regulation of aortic ICAM-1 and VCAM-1 protein expression. In this study, we found that the PI3K/Akt pathway inhibitor LY294002 weakened the PT-mediated improvement in endometrial hyperplasia, reversed the regulatory effect of PT on VEGF and eNOS expression and inhibited the increase in the proportion of EPCs. Therefore, we infer that PT may regulate intimal hyperplasia in wire-injured atherosclerotic rat carotid arteries via the PI3K/Akt pathway.
The pharmacological management of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS)
Published in Expert Opinion on Pharmacotherapy, 2020
Timothy E. Albertson, James A. Chenoweth, Skyler J. Pearson, Susan Murin
Leukotriene pathway modifiers including both leukotriene synthesis inhibitors and receptor antagonists are widely available and used in asthma and other atopic diseases. The cysteinyl leukotrienes (cys-LT) which include C4, D4 and E4 are formed by arachidonic acid precursors acted on by 5-lipoxygenase enzyme activity that then attract eosinophils and interact at cys-LT receptors on the outer plasma membrane of monocytes, macrophages, eosinophils, mast cells and smooth muscle cells of the airway [106]. Two agents that antagonize the cys-LT receptor (LRA) are available in the US and Europe (montelukast and zafirlukast) and pranlukast is also available in Japan. The second class of leukotriene pathway modulators is an inhibitor of the 5-lipoxygenase enzyme that inhibits the synthesis of both cysteinyl leukotrienes (LTC4, LTD4, and LTE4) and leukotriene B4 (LTB4) (zileuton).
Related Knowledge Centers
- Inflammation
- Reactive Oxygen Species
- White Blood Cell
- Endothelium
- Neutrophil
- Lysosome
- Chemotaxis
- Leukotriene
- Leukotriene-A4 Hydrolase
- Leukotriene A4