Neutrophil elastase metalloproteinases and their inhibitors play an important role in the development of chronic obstructive pulmonary disease (COPD) resulting in extensive tissue damage and malfunctioning of the airways. elastase pathogenesis treatment Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease (COPD) is one of the U-69593 major health care problems in the present world. The global prevalence of COPD in adults 40 years or older is usually approximately 9-10% and is higher in smokers than in non-smokers and higher in men than in women (Halbert et al 2006). COPD is an important cause of death in many countries and the incidence is still increasing because of the expanding epidemic of smoking and the progressively aging populace (Chapman et al 2006). Because of its increasing incidence the World Health Business (WHO) in collaboration with the US National Institutes of Health created the Global Initiative for chronic obstructive lung disease (Platinum). The Platinum definition explains COPD as ‘A disease state characterized by airflow U-69593 limitation that is not fully reversible and that is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases’ (Pauwels et al 2001). Classically COPD entails the three morphological forms chronic bronchitis emphysema and small airway disease. However these pathologic entities can be present in mixed forms in the same patient (Jeffery 2001). Chronic bronchitis is usually characterized by cough with expectoration due to mucus hypersecretion which does not always lead to airway obstruction. Goblet cell hyperplasia is Rabbit polyclonal to P4HA3. usually observed in the bronchial wall but the excessive mucus production correlates poorly with the mucus gland mass (Yoshida and Tuder 2007). Emphysema is usually characterized by a permanent air flow space enlargement due to a process of alveolar destruction and is not associated with significant fibrosis (Snider et al 1985 1986 Damage to the alveolar wall and attachment destruction leads to the loss of elastic recoil. You will find two major types of emphysema according to the distribution within the acinus: centrolobular and panlobular. The centrolobular form entails dilatation and destruction of the respiratory bronchioles while the panlobular form of emphysema entails the destruction of the whole of the acinus. The former is the most common type of emphysema in COPD and is more prominent in U-69593 the upper zones while the latter predominates in patients with α1-antitrypsin deficiency and is more prominent in the lower zones. COPD and Inflammation All these morphological forms of COPD chronic U-69593 bronchitis small airway disease and U-69593 emphysema are accompanied by airway inflammation. The inflammatory cell profile in the alveolar walls and the air flow spaces is similar to that explained in the airways and persists throughout the course of the disease (Finkelstein et al 1995). An increase in neutrophils macrophages and T-lymphocytes in various parts of the lung is usually characteristic and relates to the degree of airflow limitation (Saetta et al 1998). There may be an increase in eosinophils in some patients as well particularly during exacerbations (Saetta et al 1994 1996 These inflammatory cells are capable of releasing a variety of cytokines and inflammatory mediators. In addition the airway epithelium is usually a rich source of cytokines and chemokines that recruit both neutrophils and macrophages into the airspaces. Many of these cytokines are overexpressed in COPD (Chung 2001; MacNee 2007). The pro-inflammatory cytokines IL-1β and TNF-α are released by airway epithelial cells during inflammatory reactions induced by contamination injury or smoking cigarettes. Both cytokines share biological functions through some common transmission transduction pathways (Stewart and Marsden 1995). The expression of metalloproteinases and other enzymes involved in the degradation of connective tissue proteins is usually stimulated by U-69593 IL-1β in close connection with TNF-α (Cao et al 1996; Churg et al 2002 2003 2004 Kusano et al 1998). The neutrophils release a large array of serine proteases including elastase proteinase-3 and cathepsin G all are able to induce emphysema in animal models (Stockley 1983) by destroying the elastin and components of the.