HNE
Human leukocyte elastase, which is also referred to as neutrophil elastase (HLE or HNE; EC 3.4.21.47), is a highly cationic, broad-spectrum serine protease (30 kDa) primarily located in the azurophil granules of polymorphonuclear leukocytes in very high concentrations. The serine proteinase is a member of the same family as chymotrypsin and preferentially cleaves substrates C-terminally to small hydrophobic residues[1]. Under normal circumstances, the proteolytic activity of HLE is effectively controlled by its natural inhibitors. However, an imbalance between elastase and its endogenous inhibitors may result in several pathophysiological states such as chronic obstructive pulmonary disease, asthma, emphysema, cystic fibrosis, and chronic inflammatory diseases. It is anticipated that an orally active HLE inhibitor could be useful for the treatment of these diseases[2]. HLE also participates in direct intracellular killing of phagocytosed bacteria in phagolysosomes in combination with myeloperoxidase and reactive oxygen species generated by the NADPH oxidase complex. It exerts its antimicrobial activity on Gram-negative bacteria by cleaving the outer membrane protein A[3].
[1] U. Meyer-Hoffert et al. Human leukocyte elastase induces keratinocyte proliferation by epidermal growth factor receptor activation. J. Invest. Dermatol. 2004, 123, 338-345.
[2] J. Pharmacol. Exp. Ther. 2003, 305, 451-459. Z. Kapui et al. Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071), a novel, orally active elastase inhibitor.
[3] B. Korkmaz et al. Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases. Pharmacol .Rev. 2010, 62, 726-759.