Data for this review were identified by searches of MEDLINE, PubMed, and references from relevant articles using the search terms “neutrophil elastase”, “alpha-1 antitrypsin”, “alpha-1 antitrypsin deficiency”, “tumor genesis”, and “tumor progression”. Abstracts and reports from meetings were included when they related directly to previously published work, and book chapters were included if they were pertinent to the search terms. Only papers published in English between 1963 and 2003 were
ReviewRole of imbalance between neutrophil elastase and α1-antitrypsin in cancer development and progression
Section snippets
Serum concentrations
α1-antitrypsin is a secretory glycoprotein produced in the liver that neutralises the effects of proteases in several organ systems, mainly in the lung. The major physiological role of α1-antitrypsin in the lung is to bind and inhibit elastase, mainly elastase released from leucocytes in the lower respiratory tract, and thereby prevent the destruction of lung tissue.9 Concentrations of α1-antitrypsin as a mendelian codominant trait is determined by the protease inhibitor locus on chromosome
Serum concentration
Neutrophil elastase, also called serine elastase, leucocyte elastase, polymorphonuclear leucocyte elastase, or granulocyte elastase, is a serine hydrolytic protease (EC 3.4.21.37) secreted mainly by neutrophils. It is synthesised in neutrophil cell precursors in bone marrow and is encapsulated in the azurophil granules. On activation of the neutrophil, neutrophil elastase is rapidly released from the granules into the extracellular space. This single-chain glycoprotein with 218 aminoacid
Mechanisms underlying the imbalance in development and progression of cancer
Several potential mechanisms have been postulated to underlie the role of an imabalance between neutrophil elastase and α1-antitrypsin in cancer development and progression. They can be summarised in the following four aspects (figure 3)
Conclusion
The homozygous α1-antitrypsin-deficiency gene causes early onset of emphysema, especially for patients who smoke.1, 2, 3 Because of the shortened life span (median survivals were less than 45 and 65 years for smokers and those who had never smoked, respectively)35 and restrained exposure to cigarette smoking, no increased lung cancer risk is reported in these patients. Chronic liver disease occurs at a much younger age for 10% of homozygous α1-antitrypsin-deficiency gene patients19 and a third
Search strategy and selection criteria
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Structure-activity relationships of dihydropyrimidone inhibitors against native and auto-processed human neutrophil elastase
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2022, Respiratory Medicine Case ReportsHyperactive neutrophils infiltrate vital organs of tumor bearing host and contribute to gradual systemic deterioration via upregulated NE, MPO and MMP-9 activity
2022, Immunology LettersCitation Excerpt :In our study, we observed an increase in NE in peripheral blood neutrophils (Fig. 4) and in the vital organs of tumor bearing mice at both transcriptional and translational level (Fig. 5). NE was also found to be elevated in human ARDS samples, and its inhibition further resulted in reduced epithelial injury in animal models [82, 84]. Also, Baines et al. correlated high gene expression of neutrophil elastase with over-activation of neutrophils in neutrophilic asthma [85].
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