Elastase inflammatory response

Inflammatory cells produce profeases, which allow the cells to enter the affected area. Some pathogens also produce proteases in order to enter the body. Human milk contains active protease inhibitors (e.g., ot-1-antitr) sin, a-l-antichymotr) sin, and elastase inhibitor) that can limit the ability of pafhogens fo gain enfry info fhe body and limit the inflammation caused by the inflammatory response (Lindberg et al., 1982). 

Some of the effects of products of the respiratory burst would appear to have opposing effects on the inflammatory response. Neutrophils stimulated with an antigen-antibody complex or by an enzymic source of Of inactivated the elastase-inhibitory activity in serum Inactivation was prevented by both catalase and... 

Finally, serine protease from parasites and pathogens can mimic the biological roles of proteases in normal cells. Release of protease from parasites and pathogens can activate cells and produce an inflammatory response. Many pathogens and parasites contain cathepsins and elastases along with many of other serine or serine-like proteases like Streptomyces griseus A or B and a-lytic protease that lead to the invasion of abnormal cells and tissue... 

PMN Products - Neutral proteinases of PMN lysosomes degrade a wide variety of collective tissue substrates including elastin, proteoglycan, and collagen. Cathepsin G has been found only in PMN, and elastase from these cells has a substrate gpecificity different from that of pancreatic and macrophage elastase. In addition to their effects on connective tissue components, the neutral proteinases of PMN lysosomes also stimulate the activity of other cells involved in the inflammatory response. Both elastase and cathepsin G from human PMN stimulate the incor- poration of thymidine by human peripheral blood and splenic lymphocytes. The stimulated lymphocytes are of the B lineage, with no effect seen on T lymphocytes. 

While changes in the expression of pro- and anti-inflammatory cytokines and chemokines are clearly important in the initiation and maintenance of the inflammatory response in the airways, neutrophils also play a key role in the amplification of the inflammatory response. Neutrophils contribute to airway inflammation in several active ways, including the production of oxygen free radicals, the secretion of granule-associated enzymes (including neutrophil elastase), and the production of pro-inflammatory cytokines and chemokines (reviewed in 117). BAL studies of patients with cystic fibrosis have revealed the presence of abundant levels of neutrophil elastase, both complexed with a 1-antiprotease and as free elastase, compared to control subjects (70,118,119). 

Human leucocyte elastase (HE) is released in response to inflammatory stimuli and is responsible for degradation of connective tissues and is implicated in respiratory distress syndrome, rheumatoid arthritis, chronic bronchitis, and pulmonary emphysema. Many inhibitors of HE have been described [5], usually of the electrophilic carbonyl type, and often the key Val-Pro-Val motif has been exploited for potent inhibitory activity (3 - 5, Fig. 3). Recently, sivelestat (6, HE IC50 = 44 nM), a member of an enzyme-acylating series, has been approved in Japan for the treatment of acute lung injury [6]. 

Acute Phase Response. In inflammatory or necrotic processes, serum AAT levels begin to rise after approximately 24 hours and peak at 3 to 4 days if the insult is acute and short lived. Synthesis is stimulated by cytokines, particularly the IL-6 family, and by AAT-elastase complexes taken up via SEC-R. Cytokines induce a broader APR, whereas uptake by the SEC-R induces only AAT synthesis. The acute phase response of AAT probably occurs in an attempt to control... 

Triterpenes are widely distributed in plants, and in many cases are the principles responsible for their anti-inflammatory effects. Many of these compounds are active in different in vivo experimental models such as hind paw edema induced by carrageenan, serotonin and phospholipase A2 ear edema induced by phorbol and daphnane esters, ethylphenylpropiolate, arachidonic acid and capsaicin adjuvant arthritis and experimental models of allergy. Other effects have been studied in vitro, and some triterpenes are active against inflammatory enzymes like 5-lipoxygenase, elastase and phospholipase A2. Others inhibit histamine, collagenase and interleukin release, lipid peroxidation and free radical-mediated processes, metabolism of endogenous corticoids, and complement and protein-kinase activities. 

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