Regulation of airway neurogenic inflammation by neutral endopeptidase

Airway neurogenic inflammation is caused by tachykinins released from perip heral nerve endings of sensory neurons within the airways, and is character ized by plasma protein extravasation, airway smooth muscle contraction and increased secretion of mucus, Tachykinins are degraded and inactivated by neutral endopeptidase (NEP), a membrane-bound metallopeptidase, which is located mainly at the surface of airway epithelial cells, but is also present in airway smooth muscle cells, submucosal gland cells and fibroblasts. The key role of NEP in limiting an d regulating title neurogenic inflammation provoked by different stimuli ha s been demonstrated in a large series of studies published in recent pears, If has also been shown that a variety of factors, which are relevant for a irway diseases, including viral infections, allergen exposure, inhalation o f cigarette smoke and other respiratory irritants, is able to reduce NEP ac tivity, thus enhancing the effects of tachykinins within the airways. On the basis of these observations, the reduction of neutral endopeptidase activity may be regarded as a factor that switches neurogenic airway respon ses from their physiological and protective functions to a detrimental role that increases and perpetuates airway inflammation, However, Further studi es are needed to assess the role of neutral endopeptidase down regulation i n the pathogenesis of asthma and other inflammatory airway diseases.