Abstract
During inflammatory episodes neutrophils are recruited to the site of injury where they function as scavengers by killing bacteria and ingesting and degrading foreign and damaged human proteins. As a consequence of these processes significant quantities of neutrophil proteins are released extracellularly, both through cell leakage and cell death. This places a heavy burden on normal, healthy tissues which may now become susceptible to attack by neutrophil-derived oxidizing agents (myeloperoxidase-derived) and proteinases [primarily elastase (HNE) and cathepsin G (cat G)]. It is not clear as to how the body regulates the activity of myeloperoxidase, although it is likely that this involves the use of catalase in order to reduce H2O2 levels; however, to offset the possibility of protei-nase damage the body offers a series of inhibitors, primarily plasma derived, which function to specifically inactivate these enzymes. In particular, it is now known that human plasma α1 proteinase inhibitor (α1PI) regulates the activity of HNE while cat G is controlled by α1 antichymotrypsin (α1Achy).2
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Travis J., Salvesen G.: Human Plasma Proteinase Inhibitors. Ann. Rev. Biochem. 1983; 83: 655–709
Beatty K., Bieth J., Travis J.: Kinetics of Association of Serine Proteinases with Native and Oxidized Alpha-1-Proteinase Inhibitor and Alpha-l-Antichymotrypsin. J. Biol. Chem. 1980; 255: 3931–3936
Jeppson J.: Amino acid Substitution (Glu to Lys) in Alpha-l-Antitrypsin PiZ. FEBS Letters 1976; 65: 195–197
Laurell C.B., Eriksson S.: The Electrophoretic Alpha-1 -Globulin Pattern in Alpha-l -Antitrypsin Deficiency. Scand. J. Clin. Lab. Invest. 1963; 15: 132–140
Janoff A., Carp H.: Possible Mechanisms of Emphysema in Smokers. Am. Rev. Respir. Di s. 1979; 116: 65–72
Travis J., Dubin A., Potempa J., Watorek W., Kurdowska A.: Neutrophil Proteinases: Caution signs in designing inhibitors against enzymes with possible multiple functions. Ann. N.Y. Acad. Sci. 1991; 624: 81–86
Farley D., Travis J., Salvesen G.: The human neutrophil elastase gene: analysis of the nucleotide sequence. Hoppe-Seyler’s Z. Physiol. Chem. 1989; 370: 737–744
Loebermann H., Tokuoka R., Deisenhofer J., Huber R.: Human Alpha-1-Proteinase inhibitor: Crystal structure analysis of two crystal modifications, molecular modeling, and preliminary analysis of the implications for function. J. Mol. Biol. 1984; 177: 531–556
Sinha S., Watorek W., Kan S.S., Giles P.J., Bode W., Travis J.: Primary structure of human neutrophil elastase. Proc. Natl. Acad. Sci. USA 1987; 84: 2228–2232
Johnson D., Travis J.: Structural evidence for methionine at the reactive site of human Alpha-1- proteinase inhibitor. J. Biol. Chem. 1978; 253: 7142–7145
Beatty K., Matheson N., Travis J.: Kinetic and chemical evidence for the inability of oxidized alpha-l-proteinase inhibitor to protect lung elastin from elastolytic degradation. Hoppe-Seyler’ s Z. Physiol. Chem. 1984; 365: 731–736
Matheson N., Janoff A., Travis J.: Enzymatic oxidation of alpha-l-proteinase inhibitor in abnormal tissue turnover. Mol. Cellular Biochem. 1982; 45: 65–77
Morii M., Travis J.: Amino acid sequence at the reactive site of human alpha-l-antichymotrypsin. J. Biol. Chem. 1983; 258: 12749–12753
Carrell R., Travis J.: Alpha-l-Antitrytpsin and the Serpins: Variation and Countervariation. TIBS 1985; 10: 20–24
Kress L., Kurecki T., Chan S.K., Laskowski M.Sr.: Characterization of the inactive fragments resulting from limited proteolysis of human alpha-l -proteinase inhibitor by Crotalus Adamanteus proteinase II. J. Biol. Chem. 1979; 254: 5317–5320
Banda M., Sinha S., Travis J.: Inactivation of human alpha-l-Proteinase inhibitor by macrophage elastase. J. Clin. Invest. 1987; 79: 1314–1318
Boudier C., Holle C., Bieth J.: Stimulation of the elastolytic activity of leukocyte elastase by leukocyte cathepsin G. J. Biol. Chem. 1981; 256: 10256–10258
Reilly C.F., Funkunaga Y., Powers J.C., Travis J.: Effect of neutrophil cathepsin G on elastin degradation by neutrophil elastase. Hoppe-Seyler’s Z. Physiol. Chem. 1984; 365: 1131–1135
Roughley P., Barrett A.J.: The degradation of cartilage proteoglycans by tissue proteinases. Proteoglycan structure and its susceptibility to proteolysis. Biochem. J. 1977; 167: 6229–6637
Odeberg H., Olsson I.: Microbicidal mechanisms of human granulocytes: synergistic effects of granulocyte elastase and myeloperoxidase or chymotrypsin-like cationic protein. Infect. Immun. 1976; 14: 1276–1283
Bangalore N., Travis J., Onunka V., Pohl J., Shafer W.M.: Identification of the primary antimicrobial domains in human neutrophil cathepsin G. J. Biol. Chem. 1990; 265: 13584–13588
Gauldie J., Northemann W., Fey G.H.: IL-6 functions as an exocrine hormone in inflammation. Hepatocytes undegoing acute phase responses require exogenous IL-6. J. Immunol. 1990; 144: 3804–3808
Kurdowska A., Travis J.: Acute phase protein stimulation by alpha-1 -antichymotrypsin/cathepsin G complexes. Evidence for the involvement of interleukin-6. J. Biol. Chem. 1991; 265: 21023–21029
Dwenger A., Tost P., Hole W.: Evaluation of elastase and alpha-l-proteinase inhibitor-el astase uptake by polymorphonuclear leukocytes and evidence of an elastase-specific receptor. J. Clin. Chem. Clin. Biochem. 1986; 24: 299–308
Thornton A., Strieter R., Lindley I., Baggiolini M., Kunkel S.: Cytokine-induced gene expression of a neutrophil chemotactic factor/IL-8 in human hepatocytes. J. Immunol. 1990; 144: 2609–2613
Banda M., Rice A., Griffin G., Senior R.: Alpha-l-proteinase inhibitor is a neutrophil chemoattractant after proteolytic inactivation by macrophage elastase. J. Biol. Chem. 1988; 263: 4481–4484
Banda M., Rice A., Griffin G., Senior R.: The inhibitor complex of human alpha-1-proteinase inhibitor and human leukocyte elastase is a neutrophil chemoattractant. J. Exp. Med. 1988; 167: 1608–1615
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer-Verlag London
About this chapter
Cite this chapter
Travis, J., Potempa, J., Bangalore, N., Kurdowska, A. (1992). Multiple Functions of Neutrophil Proteinases and their Inhibitor Complexes. In: Grassi, C., Travis, J., Casali, L., Luisetti, M. (eds) Biochemistry of Pulmonary Emphysema. Current Topics in Rehabilitation. Springer, London. https://doi.org/10.1007/978-1-4471-3771-9_6
Download citation
DOI: https://doi.org/10.1007/978-1-4471-3771-9_6
Publisher Name: Springer, London
Print ISBN: 978-1-4471-3773-3
Online ISBN: 978-1-4471-3771-9
eBook Packages: Springer Book Archive