Cystic fibrosis patients suffer from chronic lung infection and inflammation due to the secretion of viscous sputum. Sputum viscosity is caused by extracellular DNA, some of which originates from the release of neutrophil extracellular traps (NETs). During NET formation neutrophil elastase (NE) partially processes histones to decondense chromatin. NE is abundant in CF sputum and is thought to c...

Type 1 diabetes (T1D) is an autoimmune disease resulting from the self-destruction of insulin-producing β-cells. Reduced neutrophil counts have been observed in patients with T1D. However, the pathological roles of neutrophils in the development of T1D remain unknown. Here we show that circulating protein levels and enzymatic activities of neutrophil elastase (NE) and proteinase 3 (PR3), both o...

T he contribution of the neutrophil-derived serine protease neutrophil elastase (NE) to lung disease in cystic fibrosis (CF) is unquestioned and yet, despite promising preliminary studies in the last 20 yrs to investigate an effective therapy to negate the damaging effect of NE [1], this treatment has failed to take off for patients with CF. This is largely due to the scarcity of clinical trial...

Neutrophil extracellular traps (NETs) extruded from neutrophils upon activation are composed of chromatin associated with cytosolic and granular proteins, which ensnare and kill microorganisms. This microbicidal mechanism named classical netosis has been shown to dependent on reactive oxygen species (ROS) generation by NADPH oxidase and also chromatin decondensation dependent upon the enzymes (...

The combined observations that (1) an inherited deficiency activity was found to be most strongly related to smoking, confirming previous studies. Interestingly, there was no of the major serum neutrophil elastase inhibitor, a1-proquantitative relationship between the enzyme levels, loss teinase inhibitor (a1-PI; a1-antitrypsin) predisposes to deof lung function, or degree of emphysema. Since t...

Neutrophil extracellular traps (NETs) composed of DNA decorated with histones and proteases trap and kill bacteria but also injure host tissue. Here we show that during a bloodstream infection with methicillin-resistant Staphylococcus aureus, the majority of bacteria are sequestered immediately by hepatic Kupffer cells, resulting in transient increases in liver enzymes, focal ischaemic areas an...

Neutrophils contain granules loaded with antimicrobial proteins and are regarded as impermeable organelles that deliver cargo via membrane fusion. However, during the formation of neutrophil extracellular traps (NETs), neutrophil elastase (NE) translocates from the granules to the nucleus via an unknown mechanism that does not involve membrane fusion and requires reactive oxygen species (ROS). ...

Ozone-induced airway hyperresponsiveness occurs concurrently with neutrophilic inflammation and epithelial injury in various species including humans. The mechanism of neutrophil-induced airway hyperresponsiveness, however, has not yet been fully clarified. Neutrophil elastase (NE) is a multipotent protease released from activated neutrophils, which may play a role in ozone-induced airway hyper...

Elastase/anti-elastase imbalance is a hallmark of emphysema, a chronic obstructive pulmonary disease associated with the rupture and inefficient repair of interstitial elastin. We report that neutrophil elastase (NE) at low physiologic concentrations, ranging from 35 nm to 1 microm, invokes transient, peaking at 15 min, activation of extracellular signal-regulated kinases 1 and 2 (ERK) in elast...

Extracellular proteolysis of basement membranes and matrix is required for leukocyte diapedesis and migration to the inflammatory focus. Neutrophil elastase (NE) and matrix metalloproteinases (MMPs) are among the enzymes involved in these processes, as shown in mice genetically deprived of such enzymes. However, studies with MMP-9(-/-) mice revealed that albeit neutrophil influx is impaired ini...