Anaphylaxis
Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial in Textbook of Allergy for the Clinician, 2021
Arachidonic acid metabolites derived from membrane phospholipids generate pro-inflammatory mediators such as cysleukotrienes (CysLTs), prostaglandins and PAF that can be released during anaphylaxis. Studies have shown that circulating levels of leukotrienes (LTB4, LTC4, and LTD4) increase during anaphylaxis, and are involved in enhanced vascular permeability and bronchoconstriction (Reber et al. 2017). Prostaglandin D2 (PGD2), also released from activated mast cells, promotes vasodilation, vasopermeability and airway smooth muscle bronchoconstriction (Hardy et al. 1984). The role of PAF in anaphylaxis in humans is still not well defined, however studies suggest that PAF and platelet-activating factor acetylhydrolase (PAF-AH) activity are increased in anaphylaxis, and that PAF-AH is inversely correlated with anaphylaxis severity (Vadas et al. 2013).
Nasal problems in the athlete
John W. Dickinson, James H. Hull in Complete Guide to Respiratory Care in Athletes, 2020
In a sensitised individual, upon sufficient allergen exposure at the nasal mucosa, allergen molecules bind and cross-link allergen-specific IgE bound to the surface of mucosal mast cells (Figure 8.1). Sufficient cross-linking results in signal transduction via the high-affinity IgE receptor FcεR1 which leads to mast cell activation and release of secretory granules. These granules contain a number of preformed mediators, such as histamine which stimulates sensory nerve endings within seconds, causing itch and sneezing, dilatation of local vasculature and glandular secretion, leading to nasal blockage and rhinorrhoea. Prostaglandin D2 (PGD2), also released from mast cell granules, is a vasodilator and also promotes influx of T-cells, eosinophils, and basophils. Concurrently, allergen is also taken up by antigen-presenting cells, such as dendritic cells, and presented to T cells. These T-helper 2 type cells secrete interleukins 4 and 13, which stimulate further IgE production from B cells and increased mucous secretion, plus interleukin 5 which stimulates eosinophil recruitment and activation (Figure 8.1). Eosinophils contribute to mucosal damage and inflammation through the release of highly cationic and basic proteins from intracellular granules including ECP (eosinophil cationic protein).
Exercise-Induced Bronchoconstriction
Jonathan A. Bernstein, Mark L. Levy in Clinical Asthma, 2014
Chromones are mast cell stabilizing medications that block EIB.111 These agents, including sodium cromoglycate and nedocromol sodium, are administered by inhalation, immediately prior to exercise, to provide up to 60% inhibition of EIB; but they are no longer available in the United States.111 Complete inhibition of EIB is defined as a fall in FEV1 postexercise of no more than 10%.1,2 The duration of these agents’ protection is usually less than 4 h, but their onset of action is immediate so they can be inhaled just prior to exercise on an as-needed basis.2,112 Tolerance has not been reported to the recurrent administration of these drugs. These agents reportedly work by inhibiting the release of prostaglandin D2 and leukotrienes.112 Unfortunately, the armamentarium of medications to treat EIB has been significantly weakened since these agents are no longer available.
Investigational drugs targeting prostaglandin receptors for the treatment of glaucoma
Published in Expert Opinion on Investigational Drugs, 2018
Artemis Matsou, Eleftherios Anastasopoulos
Prostaglandin D2 (PGD2) elicits its responses by activating one of the two receptors DP1 or DP2. Although largely involved in ocular immune responses, DP receptor agonists were also found to have significant IOP lowering effect in animal studies [66,67]. The selective synthetic DP prostaglandin receptor agonist, BW 245C was reported to lower IOP in rabbits, however when tested in humans, it produced intense acute conjunctival hyperemia [68] and has since been abandoned due to its side effects. Similar results were found for other DP prostaglandin agonists such as SQ-27986 [69], BW 572C85, and BW 192C86. AL–6598, the isopropyl ester prodrug of AL-6556, is a DP/EP2 receptor agonist that was shown to produce a 53% IOP drop in cynomolgus monkeys in a twice daily regime [70], while in humans resulted in a sustained reduction in IOP of more than 27% [71]. Significant conjunctival hyperemia was again noted but with no signs of intraocular inflammation. Another study in normotensive monkey eyes by Torris et al., demonstrated that AL-6598, has a dual effect on aqueous humor dynamics; both an increase in aqueous humor production, which is an undesired consequence, and an increase in aqueous humor drainage via the uveoscleral pathway [71]. Since then, there is a paucity of data and new research in DP agonists for glaucoma, and quite reasonably so, since more potent molecules with fewer side effects have come to light.
Autoantibodies in Pandemrix®-induced narcolepsy: Nine candidate autoantigens fail the conformational autoantibody test
Published in Autoimmunity, 2019
Madeleine Wallenius, Alexander Lind, Omar Akel, Emma Karlsson, Markus Svensson, Elin Arvidsson, Anita Ramelius, Carina Törn, Lars Palm, Åke Lernmark, Helena Elding Larsson
Other suggested NT1 autoantigens include Tribbles homologue 2 (TRIB2) [17–20], α-melanocyte stimulating hormone (α-MSH) [21], Prostaglandin D2 Receptor DP1 (DP1) [22], methyltransferase-like 22 (METTL22) and 5′-nucleotidase cytosolic 1A (NT5C1A) [23]. The suggestions of non-hypocretin neuron-specific autoantigens are of interest when considering alternative pathogenic mechanisms behind NT1 as opposed to a direct immune-attack against these cells. Both α-MSH and DP1 have known implications to NT1-associated side-effects. α-MSH is presumed to be involved in weight homeostasis by inhibiting feeding behaviour [24]. NT1 patients are known to have a higher risk to develop obesity and other metabolic problems associated with the loss of hypocretin neurons [25]. Among its many functions in the central nervous system, DP1 is known to be involved in the regulation of sleep through its activation by prostaglandin D2, a sleep-promoting substance [22].
Moving toward consensus on diagnosis and management of severe asthma in adults
Published in Current Medical Research and Opinion, 2018
Daniel Colodenco, Oscar Palomares, Carlos Celis, Alan Kaplan, Christian Domingo
As described earlier, eosinophils are known major inflammatory cells involved in the pathophysiology of asthma. These also play a role in airway remodeling through production and expression of several fibrogenic factors, particularly transforming growth factor (TGF)-β157. The cytokine IL-5 primarily drives eosinophil proliferation, maturation, activation, and survival, which are associated with severe, difficult-to-treat asthma58. Furthermore, IL-13 stimulates eosinophilic airway inflammation and promotes mucus metaplasia, subepithelial fibrosis, and airway remodeling59. While in the lung, eosinophils stimulate secretion of cytokines (IL-13 IL-5, TGF-β, and osteopontin), chemokines (CCL-11, CCL22, matrix metalloproteinases [MMPs] and granule mediators [e.g. erythropoietin and major basic protein]), and leukotrienes (LTC4 and LTB4)60. Recently, prostaglandin D2 (PGD2) has been shown to play a vital role in mediating eosinophilic airway inflammation in asthma through stimulation of Th2 cell migration, delayed Th2 cell apoptosis, and production of IL-4, IL-5, and IL-1361. Periostin, a matricellular protein, has also been implicated in eosinophil recruitment62.
Related Knowledge Centers
- Asthma
- Basophil
- T Helper Cell
- Allergy
- Prostaglandin
- Brain
- Prostaglandin D2 Receptor
- Prostaglandin Dp2 Receptor
- Mast Cell
- Eosinophil