Controlled release proteinases

Serine proteases, released from immune cell granules, process cytokines and growth factors that control multiple cellular process [56], Proteinase 3, cathepsin G, and elastase all cleave membrane-bound TNF-o, IL-1, and IL-18, and activate epidermal growth factor receptor (EGFR) and toll-like receptor-4 (TLR-4). These actions inhibit growth and lead to apoptosis with transcriptional nuclear factor kB (NF-kB) inactivation. Bik suppresses release of TNF-o, IL-1, and IL-18 and prevents EGFR and TLR-4 activation. Activation of NF-kB is a mediator of cell proliferation, whereas inhibition of NF-/. B leads to apoptosis [82]. Overall, Bik inhibition of immune cell serine proteases increases cell proliferation and stability. 

Due to its broad specificity and high concentrations within neutrophils. NE has been implicated in the development and progression of several lung diseases such as pulmonary emphysema, cystic fibrosis, adult respiratory distress syndrome, and chronic bronchitis [2-4]. During phagocytosis and neutrophil turnover, there is a release of elastase into the extracellular environment which, if not controlled, can result in extensive damage to connective tissue. The destructive effect of elastase is normally controlled by endogenous proteinase inhibitors... 

A recent study reports the release profile of the Serp-1 proteinase from PVA-C [65]. Serp-1 is a serine proteinase inhibitor (serpin) secreted by the myxoma vims and is a potential new therapeutic for cardiovascular diseases. It has exhibited antiinflammatory activity through the modulation of immune cell responses [66]. The release profile of this protein in a buffer medium is typical of that of a diffusion controlled process. However, it is interesting to know that the release rate of Serp-1 and its final release level attained differ in human blood and in buffer. The release rate is twice as fast and in half of the time in blood than in buffer. The final release level is complete in blood and appears to level off at around 50% in buffer. It was suggested that there may be a difference in behavior between the two release media, which is important to consider because human whole blood represents a more realistic setting of the physiological environment in arteries. It is also possible that interaction between PVA-C and blood components play a role in determining the ultimate release rate (Fig. 9a, b) [65]. 

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