Inhibitor Of Neutrophil Proteinases Elafin Expression In Pichia Pastoris And Activity Investigation

Generally ,neutrophil elastase (NE) acts as an alexin to degrade invaded bacterium and assist neutrophils to migrate to inflammatory sites.However,the massive accumulation of stimulated polymorpho-nuclear neutrophils(PMNs) at the site of inflammation is accompanied by lysis of these inflammatory cells resulting in the extracellular release of a variety of hydrolases and oxidases.More specifically,three serine proteases including human leukocyte elastase,cathepsin G and proteinase 3,are simultaneously released at high concentrations .All three of these serine proteinases participate in the destruction fo lung tissues by degrading numerous extracellular matrix proteins such as elastin,type III,IV collagens, fibronectin,laminin, etc. Inflammatory lung disease such as chronic obstructive pulmonary disease ( COPD ),acute lung injury ( ALI ),acute respiratory distress syndrome ( ARDS ),cystic fibrosis ( CF ) have been known as the consequence of a protease-antiprotease imbalance. Furthermore,these proteases stimulate mucous secretion by submucosal gland serous cells and goblet cells and also promote the synthesis of inflammatory cytokines,and therefore have a major role in perpetuating the inflammatory state.Though other degrading proteases including metalloproteases ( MMP ) may be released from neutrophils,it is thought that serine proteases of neutrophil origin have the greatest contribution to the protease-antiprotease imbalance observed in lung inflammation.So to prevent massive production of serine proteinases is an important task for clinicians.Elafin is a special inhibitor to serine proteases including human leukocyte elastase,cathepsin G and proteinase 3,secreted by clara celles and type II alveolus.It's an important factor in balancing the protease-antiprotease imbalance observed in lung inflammation and furthermore to lower mucus hypersecretion caused by NE.In addition ,elafin shows broad spectrum antibiotic activity that includes gram positive and negative bacterium.Elafin also shields the tissues against pre-inflammatory products such as inteleukin-6 ( IL-6 ),IL-10,nuclear factorκB ( NF-κB),etc.For its great value,we establish expression system of elafin in Pichia pastoris to get full-length recombinant elafin.