More than destructive: neutrophil-derived serine proteases in cytokine bioactivity control

In addition to the mechanisms inducing the expression and secretion of cytokines under distinct pathophysiological conditions, the fate of cytokines after secretion at sites of inflammation is a field of growing interest. Proteolysis has been suggested to be a fundamental mechanism of regulating the activities of various components of the cytokine network. Evidence grows that besides highly specific cytokine converting proteases such as interleukin-1beta-converting enzyme or tumor necrosis factor-converting enzyme, neutrophil-derived serine proteases are intimately involved in the modulation of the activities of cytokines and their receptors. Particularly at sites of inflammation, high amounts of the active serine proteases elastase, cathepsin G, and proteinase 3 are released from infiltrating polymorphonuclear cells in close temporal correlation to elevated levels of inflammatory cytokines, strongly indicating that these proteases are involved in the control of cytokine bioactivity and availability.