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Regulatory status: For research use only, not for use in diagnostic procedures.
Neutrophil elastase (NE) is the major protein hydrolase expressed in the primary granules of neutrophils and is an important factor in promoting inflammation with bactericidal effects and shortening the inflammatory process. NE hydrolase accounts for approximately 80% of the body's total protein hydrolase activity and breaks down a variety of substances including elastin, collagen, and fibronectin. NE levels and activity reflect disease status and severity.
Human neutrophil elastase (HNE) belongs to the chymotrypsin family and is a serine protease (SP) with protein hydrolyzing activity consisting of 218 amino acid residues with two carbohydrate side chains attached to asparagine and linked by four disulfide bonds. The enzyme is encoded by the ELANE gene, mutations in which have been associated with diseases such as severe circulating congenital neutropenia. SP has a strong affinity for catalyzing the cleavage of carboxyl groups in small hydrophobic amino acids such as glycine, alanine, and valine. It also cleaves several types of proteins that make up the extracellular matrix, including fibronectin, elastin, proteoglycans, collagen, adhesion proteins, and various plasma proteins. In addition, HNE degrades soluble proteins such as coagulation factors, immunoglobulins, complement proteins and inhibitors. HNE is primarily involved in the body's immune response to invading pathogens, but it also has antimicrobial activity by disrupting the outer membranes of gram-negative bacteria, including E. coli, as well as spirochetes and fungi. Follow-up studies have found that HNE has attenuating and activating effects on antimicrobial peptides and may serve as an alternative to high resistance to chronic infections in cystic fibrosis patients. In addition to its immune-promoting function, HNE also catabolizes certain pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which negatively regulates the inflammatory process.
Figure 1. The specific process of the anti-infection effect of NE
(Source: Zeng W, et al. 2023)
Based on the role that HNE plays in the development of inflammatory diseases, researchers are searching for and developing molecules that can inhibit its activity. HNE inhibitors are endogenous molecules and exogenous chemicals, and these inhibitors can be categorized according to different principles of action and characteristics, such as reversible or irreversible inhibitors according to the nature of their interaction with the enzyme; competitive, noncompetitive, or mixed inhibitors according to the location of their binding to the enzyme; direct and indirect inhibitors according to the mechanism of action; and natural and synthetic according to the source of the inhibitors.
anti-Human NE pAb
anti-HNE pAb
References
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Causal Role for Neutrophil Elastase in Thoracic Aortic Dissection in Mice
Arterioscler Thromb Vasc Biol
Authors: Yang M, Zhou X, Pearce SWA, Yang Z, Chen Q, Niu K, Liu C, Luo J, Li D, Shao Y, Zhang C, Chen D, Wu Q, Cutillas PR, Zhao L, Xiao Q, Zhang L.
Neutrophil elastase in dexmedetomidine alleviating sepsis-related renal injury in rats
Int Immunopharmacol
Authors: Chen L, Li M, Lin Y, Li Y, Liang M, Zeng K.
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