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Mucosal basophils, eosinophils, and mast cells
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Edda Fiebiger, Stephan C. Bischoff
In addition to antibody- and cytokine-mediated activation, basophils are activated by allergens, parasite antigens, and other pathogen-associated molecules. Specifically, secretions of the hookworm parasite Necator americanus and the house dust mite antigen Derp1, which possess active protease activity, can induce the production of IL-4, IL-5, and IL-13 by human basophils. These activities are eliminated by protease inhibitors, suggesting that basophils may express protease-activated receptor-like factors that are capable of the proteolytic activation of such antigens (or organisms) and activate innate and adaptive immune cells.
Therapy of acute myocardial infarction
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Joshua M. Stolker, Michael W. Rich
Vorapaxar antagonizes the protease-activated receptor-1 on platelets, thus inhibiting thrombin-induced platelet aggregation. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2P-TIMI 50) trial evaluated vorapaxar in patients with prior MI (>2 weeks previously) or peripheral arterial disease at high risk of ischemic events (40). Vorapaxar reduced thrombotic events compared to placebo, and the drug was approved for use in the United States in 2014. However, higher bleeding rates were noted with vorapaxar, and since most patients with recent MI are already treated with aspirin and another oral antiplatelet medication, use of vorapaxar in the geriatric population may be limited to very select patients with peripheral arterial disease at low risk for bleeding.
Inhibiting Low-Density Lipoproteins Intimal Deposition and Preserving Nitric Oxide Function in the Vascular System
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
Blood pressure is the result of a balance between cardiac output and peripheral vascular resistance.122 In Metabolic Syndrome, vascular dysfunction leads to hypertension and life threatening cardiovascular and cerebrovascular diseases events.123 Aqueous extract of roots of Arbutus unedo L. given daily at a dose of 150 mg/kg to Wistar rats challenged with Nω-nitro-l-arginine methyl ester (L-NAME) lowered systolic blood pressure from 188 to 155 mmHg, reduced ventricular hypertrophy, and protected the cardiac baroreflex responsiveness to phenylephrine. The extract prevented relaxation induced by carbachol.124 Thrombin binds to protease-activated receptor-1 and receptor-6 and induces platelet activation via the activation of G protein-coupled signaling.125 Aqueous extract of leaves at a concentration of 0.05 mg/mL inhibited the aggregation of platelets induced by thrombin by 45% in vitro via inhibition of reactive oxygen species generation, influx of calcium and tyrosine phosphorylation.126
Destiny of airway disease: interplay between epithelial barrier and the innate immune system
Published in Tissue Barriers, 2022
Barrier function is maintained by adherens junctions, homophilic E-Cadherin interactions, and intercellular contact formation.34 E-Cadherin binds to the actin cytoskeleton with Beta-Catenin stabilizing cell-cell. E-Cadherin downregulation is an essential component of the epithelial-mesenchymal transition (EMT), a process involved in cell migration, repair, and tissue remodeling. Many allergens contain proteases that cause epithelial damage. Proteases can also activate the ‘protease-activated receptor’ (PAR), which leads to proinflammatory gene transcription.35 PAR activation disrupts E-Cadherin-mediated cell-cell contact. Damaged epithelium induces the mesenchymal phenotype by showing increased sensitivity to noxious stimuli and inadequate repair response. Insufficient epithelial repair marker CD44 is supported by epidermal growth factor receptor (EGFR) and increased expression of TGF-Beta in damaged epithelium.29
Enhanced intestinal permeability and intestinal co-morbidities in heat strain: A review and case for autodigestion
Published in Temperature, 2021
Anthony A. Fung, Andy Zhou, Jennifer K. Vanos, Geert W. Schmid-Schönbein
One of the consequences of such unchecked protease activity is the cleavage of membrane receptors, a process that compromises the associated cell functions they control. For example, cleavage of the adrenergic receptors may cause a central blood pressure reduction [96], an elevated permeability to molecules the size of digestive enzymes as interepithelial membrane adhesion molecules (e.g., E-cadherin) are cleaved [91,97], or insulin resistance may arise as the ectodomain of the insulin receptor is cleaved [98]. While to date, receptor cleavage has not been investigated in heat shock, it is notable that post-exertional heat stroke and even post-exercise controls exhibit hyperglycemia over several hours and days (Figure 12). One exception is the cleavage and activation of the protease-activated receptor (PAR1). Pharmacological inhibition of this receptor attenuates elevation of the intestinal permeability after heat stress (Figure 13).
Aspirin and low-dose rivaroxaban – the dual pathway concept in patients with stable atherosclerotic disease: a comprehensive review
Published in Expert Review of Cardiovascular Therapy, 2020
Eliot Parascandolo, Alon Eisen
The reasoning behind the dual pathway concept, the conjugate use of aspirin and rivaroxaban, is a rational thought. Aspirin works by attenuating platelet activation and rivaroxaban works by attenuating thrombin generation thereby working ‘via dual pathways’. It is important to inhibit both pathways because when atherosclerotic plaques get disrupted not only does this trigger platelet activation/aggregation but also induces thrombin generation via exposure to epithelial tissue factors. It was demonstrated that patients even with antiplatelet therapy had evidence of persistent coagulation which could be due to thrombin being a platelet agonist [12,13]. Thus, by inhibiting thrombin it can also be expected that platelet activation and fibrin formation would be reduced [4]. As stated, aspirin is a well-established anti-inflammatory drug, furthermore, when combined with rivaroxaban these effects become more pronounced. With inhibition of factor Xa via rivaroxaban, factor Xa activation of protease-activated receptor (PAR) and thrombin-induced activation of PAR-1 and PAR-4 is reduced. This suppresses inflammation which leads to the reduced development or further progression of atherosclerosis [4].