Alpha-1 antitrypsin, inflammation and quality of life

Abstract

Alpha-1 antitrypsin (AAT) is the main circulating serine proteinase inhibitor. A number of studies suggest that AAT can also exhibit biological activity independent of inhibition of serine proteases. The aim of the study was to make experimental investigation of AAT influence on monocytes stimulated by bacterial endotoxyn and to analyze serum AAT concentration in patients with COPD in relation to smoking. Human blood monocytes were isolated from buffy coats. Serum biomarkers from COPD patients and culture supernatants from donors monocytes were analysed using commercial ELISA kits. AAT affects monocyte responses to LPS by regulating soluble CD14 release. Here we show that a short-term (up to 2 h) monocyte exposure to AAT leads to an increase of CD14 levels (p < 0.05). In parallel, a short-term (2 h) cell exposure to AAT significantly enhances TNFα release. However, AAT was found to have a dual effect on LPS-induced TNFα release. Thus, during the first 4 h AAT enhanced, while after 8, 12, 18 and 24 h it inhibited LPS-stimulated TNFα release. COPD smokers and ex-smokers showed higher alpha-1 antitrypsin and C-reactive protein serum concentration than neversmokers (p < 0.05), that may be important for quality of life and health state. Probably a rapid increase in AAT concentrations during various inflammatory and infectious conditions may enhance the magnitude of monocyte responses to endotoxin and subsequently accelerate resolution of the inflammatory reaction.