Neutrophil serine proteases: mediators of innate immune responses

Neutrophil cells have been considered mainly as innate immune cells directed against microbial threats. Their serine proteases neutrophil elastase, proteinase 3 and cathepsin G are main constituents and are released at sites of inflammation. During recent years it became clear that neutrophil serine proteases act as regulators of cell signaling and immune regulation.

Neutrophils are able to form so-called neutrophil extracellular traps. Recent studies showed that these extracellular traps might be involved in small vessel vasculitis and lupus nephritis. Neutrophil serine proteases in concert with externalized nucleosomes promote thrombus formation inside blood vessels. This event helps retain bacteria inside liver microvessels and thereby prevents the extravasation of pathogens. Moreover, neutrophil serine proteases act as alternative processing enzymes of pro-inflammatory cytokines IL-1β and IL-18 in vivo and modulate other inflammation-related control mechanisms such as progranulin inactivation, matrix metalloproteinase-9 activation and IL-6 inactivation. Recent studies point to an involvement of neutrophil elastase in lung cancer by inducing mitogenesis after entering the cells.

The knowledge of the different functions of neutrophils is still expanding. Recent findings underline the importance of neutrophil serine proteases as key mediators of inflammatory processes and point to novel strategies against inflammatory disorders.