Passively released or actively secreted elastase from neutrophils has been linked to the pathologic processes of a variety of inflammatory diseases, including idiopathic pulmonary fibrosis, rheumatoid arthritis, adult respiratory distress syndrome, and cystic fibrosis. The serine proteinase has a broad substrate specificity and may attack a number of host proteins outside of the neutrophil, including lung elastin and fibronectin. Such a proteolysis may change the normal surrounding tissue and the protein pattern of an inflammatory focus. Additionally, it acts as a potent secretagogue in minute amounts. The reason that neutrophil elastase is present in considerable concentrations outside of the neutrophil during chronic inflammation and that the major endogenous serine proteinase inhibitor for neutrophil elastase, aI-proteinase inhibitor, is easily inactivated by proteolytic and oxidative attack is unclear. Released neutrophil elastase may also be involved in regulating chronic inflammation. In a feedback mechanism, neutrophil elastase inhibits neutrophil stimulation and concomitant elastase release by cleavage of immunoglobulins, complement components, and complement receptor type 1 on neutrophils. Besides a number of harmful effects of neutrophil elastase in inflammation, the latter mechanism, although considerably impairing phagocytosis, may be beneficial particularly in the light of persistent bacterial pathogens in the human lung affected by cystic fibrosis. Doring G. Role of neutrophil elastase in chronic inflammation. Am J Respir Crit Care Meet 1994; 150: 8114-7.

Polymorphonuclear leukocytes (or neutrophils) are specialized phagocytic cells that mature in the bone marrow, enter the bloodstream, and rapidly distribute between marginated and circulating pools. A pool size of 6.1 x 107neutrophils in normal human lungs has been extrapolated from animal data (1). Upon chemotactic stimulation via specific cell receptors, circulating neutrophils will adhere to the endothelial cells lining the blood vessels through integrins (2) and move along chemotactic gradients through the space between the endothelial cells by a process known as diapedesis in order to carry out their function. Phagocytosis involves direct recognition or receptor-mediated binding of compounds, particles, or microbes on the neutrophil cell surface, and their uptake into a phagolysosome that has been built by fusion of intracellular granules or Iysosomes with the neutrophil cell surface membrane (3). Neutrophil granules can be differentiated into specific and primary (azurophilic) granules, the latter containing the serine proteinases elastase, cathepsin G, and proteinase 3, as well as other enzymes thought to be involved in hydrolytic, proteolytic, and oxidative breakdown of the phagocytosed compound (3). According to this picture, digestion takes place intracellularly in a phagocytic vacuole filled with lysosomal enzymes and oxygen radicals.