title: Arginase: a key enzyme in the pathophysiology of allergic asthma opening novel therapeutic perspectives.
abstract: Allergic asthma is a chronic inflammatory airways' disease, characterized by allergen-induced early and late bronchial obstructive reactions, airway hyperresponsiveness (AHR), airway inflammation and airway remodelling. Recent ex vivo and in vivo studies in animal models and asthmatic patients have indicated that arginase may play a central role in all these features. Thus, increased arginase activity in the airways induces reduced bioavailability of L-arginine to constitutive (cNOS) and inducible (iNOS) nitric oxide synthases, causing a deficiency of bronchodilating and anti-inflammatory NO, as well as increased formation of peroxynitrite, which may be involved in allergen-induced airways obstruction, AHR and inflammation. In addition, both via reduced NO production and enhanced synthesis of L-ornithine, increased arginase activity may be involved in airway remodelling by promoting cell proliferation and collagen deposition in the airway wall. Therefore, arginase inhibitors may have therapeutic potential in the treatment of acute and chronic asthma. This review focuses on the pathophysiological role of arginase in allergic asthma and the emerging effectiveness of arginase inhibitors in the treatment of this disease.
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands. h.maarsingh@rug.nl
authors.forename: Harm
authors.initials: H
authors.lastname: Maarsingh
authors.forename: Johan
authors.initials: J
authors.lastname: Zaagsma
authors.forename: Herman
authors.initials: H
authors.lastname: Meurs
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001119:Arginase / Q000037:antagonists & inhibitors / Q000502:physiology*; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000502:physiology; D012143:Respiratory Physiological Phenomena
chemical_list: D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001119:Arginase
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