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. © 2009 The British Pharmacological Society.