Neutrophil elastase as an inflammatory mediator

Abstract


Neutrophils are the first cells recruited to the site of an infection. The influx of neutrophils within the sites of inflammation plays the important role in the normal human defense, but also may contribute to the pathogenesis of various disorders. They are capable of causing tissue destruction and cell death. Neutrophilic inflammation is observed in patients with a1- proteinase inhibitor deficiency, bronchitis, emphysema, ARDS, COPD, re-perfusion injury, cystic fibrosis, acute severe asthma, cigarette smoking.
The numerous data suggest that neutrophil elastase (NE) is an important mediator of the acute and chronic inflammatory response. NE perpetuates the cycle of inflammation by promoting the generation of chemoattractants, particularly interleukin-8 and leukotriene B4, which recruit more neutrophils into the tissue. The stimulation status of neutrophils in inflamed tissue can be estimated by measuring the concentration of neutrophil elastase in complex with a1-proteinase inhibitor (NE-α₁PI). The examination of plasma levels of NE- α₁PI can be used as a novel and sensitive indicator of the acute and chronic response and neutrophils activation in different diseases. The dynamic changes of the concentration of NE- α₁PI may be of diagnostic, prognostic and therapeutic importance. It seems that the determination of free NE or NE- α₁PI complex in body fluid can be accepted to the routine use in diagnostic of inflammatory state of organisms. New treatment strategies for neutrophil inflammation are being developed. Several studies demonstrate that antiprotease therapy may be effective to inhibit NE and reduce the inflammation state.