leukocyte elastase

Summary

Summary: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 3.4.21.37.

Top Publications

  1. Ho S, Lee K, Chan Y, Kuo L, Ito K, Adcock I, et al. Neutrophil elastase represses IL-8/CXCL8 synthesis in human airway smooth muscle cells through induction of NF-kappa B repressing factor. J Immunol. 2009;183:411-20 pubmed publisher
    ..Hence, we describe a novel negative regulatory mechanism of NE-induced NRF, which is restricted to hASM and mediates the suppression of IL-8/CXCL8 expression. ..
  2. Shang K, Bai Y, Wang C, Wang Z, Gu H, Du X, et al. Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice. PLoS ONE. 2012;7:e51848 pubmed publisher
    ..These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer. ..
  3. Weldon S, McNally P, McElvaney N, Elborn J, McAuley D, Wartelle J, et al. Decreased levels of secretory leucoprotease inhibitor in the Pseudomonas-infected cystic fibrosis lung are due to neutrophil elastase degradation. J Immunol. 2009;183:8148-56 pubmed publisher
    ..aeruginosa-positive CF lung secretions and that P. aeruginosa infection contributes to inactivation of the host defense screen in the CF lung. ..
  4. Fujii M, Miyagi Y, Bessho R, Nitta T, Ochi M, Shimizu K. Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass. Interact Cardiovasc Thorac Surg. 2010;10:859-62 pubmed publisher
    ..However, sivelestat attenuated the pattern of physiological deterioration of gas exchange. Sivelestat may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing CPB. ..
  5. Madoiwa S, Tanaka H, Nagahama Y, Dokai M, Kashiwakura Y, Ishiwata A, et al. Degradation of cross-linked fibrin by leukocyte elastase as alternative pathway for plasmin-mediated fibrinolysis in sepsis-induced disseminated intravascular coagulation. Thromb Res. 2011;127:349-55 pubmed publisher
    An alternative pathway for fibrinolysis that comprises leukocyte elastase and its interaction with the plasminogen activator-plasmin system has been suggested...
  6. Aimetti A, Tibbitt M, Anseth K. Human neutrophil elastase responsive delivery from poly(ethylene glycol) hydrogels. Biomacromolecules. 2009;10:1484-9 pubmed publisher
    ..The hydrogel platform presented shows highly controlled release kinetics with potential applications in cellular responsive drug delivery. ..
  7. Aimetti A, Machen A, Anseth K. Poly(ethylene glycol) hydrogels formed by thiol-ene photopolymerization for enzyme-responsive protein delivery. Biomaterials. 2009;30:6048-54 pubmed publisher
    ..Also, protein release was predicted from a 3-layered hydrogel device using mass loss data. Lastly, the bioactivity of lysozyme was maintained above 90% following the exposure to thiol-ene photopolymerization conditions. ..
  8. Thongyoo P, Bonomelli C, Leatherbarrow R, Tate E. Potent inhibitors of beta-tryptase and human leukocyte elastase based on the MCoTI-II scaffold. J Med Chem. 2009;52:6197-200 pubmed publisher
    ..possess potent activity against two therapeutically significant serine proteases: beta-tryptase and human leukocyte elastase. These results suggest that MCoTI-II is a versatile scaffold for the development of protease inhibitors ..
  9. Parameswaran G, Wrona C, Murphy T, Sethi S. Moraxella catarrhalis acquisition, airway inflammation and protease-antiprotease balance in chronic obstructive pulmonary disease. BMC Infect Dis. 2009;9:178 pubmed publisher
    ..catarrhalis as compared to colonization...

More Information

Publications76

  1. Guma M, Ronacher L, Liu Bryan R, Takai S, Karin M, Corr M. Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation. Arthritis Rheum. 2009;60:3642-50 pubmed publisher
    ..These pathways might therefore compromise the caspase 1-targeted therapies in neutrophil-predominant arthritis. ..
  2. Papareddy P, Rydengård V, Pasupuleti M, Walse B, Morgelin M, Chalupka A, et al. Proteolysis of human thrombin generates novel host defense peptides. PLoS Pathog. 2010;6:e1000857 pubmed publisher
    ..These findings provide a novel link between the coagulation system and host-defense peptides, two fundamental biological systems activated in response to injury and microbial invasion. ..
  3. Jiang D, Wenzel S, Wu Q, Bowler R, Schnell C, Chu H. Human neutrophil elastase degrades SPLUNC1 and impairs airway epithelial defense against bacteria. PLoS ONE. 2013;8:e64689 pubmed publisher
    ..Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections. SPLUNC1 therapy likely attenuates bacterial infections during AECOPD. ..
  4. Korsgren M, Linden M, Entwistle N, Cook J, Wollmer P, Andersson M, et al. Inhalation of LPS induces inflammatory airway responses mimicking characteristics of chronic obstructive pulmonary disease. Clin Physiol Funct Imaging. 2012;32:71-9 pubmed publisher
    ..The aim of this study was to further characterize the response to LPS in order to develop a human model suitable for early testing of drug candidates developed for the treatment for chronic obstructive pulmonary disease (COPD)...
  5. Wood L, Baines K, Fu J, Scott H, Gibson P. The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma. Chest. 2012;142:86-93 pubmed publisher
    ..Systemic inflammation is increased in patients with asthma with neutrophilic airway inflammation and associated with worse clinical outcomes. Systemic inflammation may contribute to the pathophysiology of neutrophilic asthma. ..
  6. Klein C, Welte K. Genetic insights into congenital neutropenia. Clin Rev Allergy Immunol. 2010;38:68-74 pubmed publisher
    ..g. p14-deficiency or G6PC3-deficiency. The clinical and genetic findings of various neutropenia syndromes are being discussed. ..
  7. Papayannopoulos V, Metzler K, Hakkim A, Zychlinsky A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol. 2010;191:677-91 pubmed publisher
  8. Bergsson G, Reeves E, McNally P, Chotirmall S, Greene C, Greally P, et al. LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline. J Immunol. 2009;183:543-51 pubmed publisher
  9. Skokowa J, Fobiwe J, Dan L, Thakur B, Welte K. Neutrophil elastase is severely down-regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF-1. Blood. 2009;114:3044-51 pubmed publisher
    ..LEF-1 rescue of CD34(+) cells isolated from 2 patients with CN resulted in granulocytic differentiation of the cells which was in line with increased levels of functionally active ELA2/NE. ..
  10. Benabid R, Wartelle J, Malleret L, Guyot N, Gangloff S, Lebargy F, et al. Neutrophil elastase modulates cytokine expression: contribution to host defense against Pseudomonas aeruginosa-induced pneumonia. J Biol Chem. 2012;287:34883-94 pubmed publisher
    ..aeruginosa-associated diseases will need to be carefully reassessed. Also, therapeutic strategies aiming at NE inhibition should take into account the physiologic roles of the enzyme. ..
  11. Mittendorf E, Alatrash G, Qiao N, Wu Y, Sukhumalchandra P, St John L, et al. Breast cancer cell uptake of the inflammatory mediator neutrophil elastase triggers an anticancer adaptive immune response. Cancer Res. 2012;72:3153-62 pubmed publisher
    ..Taken together, our findings reveal a previously unknown mechanism of antitumor adaptive immunity that links cancer cell uptake of an inflammatory mediator to an effective cytolytic response against an important breast cancer antigen. ..
  12. Jackson P, Xu X, Wilson L, Weathington N, Clancy J, Blalock J, et al. Human neutrophil elastase-mediated cleavage sites of MMP-9 and TIMP-1: implications to cystic fibrosis proteolytic dysfunction. Mol Med. 2010;16:159-66 pubmed publisher
    ..These results demonstrate increased MMP-9 activity in stable CF lung disease, and the presence of specific protease products in CF sputum highlights that HNE-mediated activity plays a role in this dysregulation. ..
  13. Vlahos R, Wark P, Anderson G, Bozinovski S. Glucocorticosteroids differentially regulate MMP-9 and neutrophil elastase in COPD. PLoS ONE. 2012;7:e33277 pubmed publisher
    ..Furthermore, as NE and MMP-9 release was resistant to GC, targeting of the PI3K pathway may offer an alternative pathway to combating this proteinase imbalance in severe COPD. ..
  14. Cosgrove S, Chotirmall S, Greene C, McElvaney N. Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression from bronchial epithelial cells via a heme/meprin/epidermal growth factor receptor/Toll-like receptor pathway. J Biol Chem. 2011;286:7692-704 pubmed publisher
    ..This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention. ..
  15. Xia J, Bolyard A, Rodger E, Stein S, Aprikyan A, Dale D, et al. Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia. Br J Haematol. 2009;147:535-42 pubmed publisher
    ..In patients without ELANE mutations, other known SCN-associated gene mutations will be found rarely and genotyping can be guided by the clinical features of each patient. ..
  16. Xu Y, Zhang J, Han J, Pan X, Cao Y, Guo H, et al. Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of ?1-antitrypsin in lung cancer. Mol Oncol. 2012;6:405-17 pubmed publisher
  17. Dubois A, Gauthier A, Bréa D, Varaigne F, Diot P, Gauthier F, et al. Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum. Am J Respir Cell Mol Biol. 2012;47:80-6 pubmed publisher
    ..Combining the effects of protease inhibitors with that of DNA-degrading agents could counter the deleterious proteolytic effects of NSPs in CF lung secretions. ..
  18. Houghton A. The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances. Cell Cycle. 2010;9:1732-7 pubmed
    ..Alternatively, strategies designed to generate highly activated and cytotoxic neutrophils within the tumor microenvironment may provide a means to unleash the tumoricidal potential of the host's innate immune response. ..
  19. Massberg S, Grahl L, von Bruehl M, Manukyan D, Pfeiler S, Goosmann C, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010;16:887-96 pubmed publisher
    ..The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense. ..
  20. Yu H, Hsieh P, Chang Y, Chung P, Kuo L, Hwang T. 2-(2-Fluorobenzamido)benzoate ethyl ester (EFB-1) inhibits superoxide production by human neutrophils and attenuates hemorrhagic shock-induced organ dysfunction in rats. Free Radic Biol Med. 2011;50:1737-48 pubmed publisher
    ..Therefore, EFB-1 is a new inhibitor of cAMP-specific PDE that potently suppresses O(2•-) release and CD11b expression by human neutrophils and attenuates T/H-induced MOD in rats. ..
  21. Joosten L, Netea M, Fantuzzi G, Koenders M, Helsen M, Sparrer H, et al. Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta. Arthritis Rheum. 2009;60:3651-62 pubmed publisher
  22. Alexiou K, Matschke K, Westphal A, Stangl K, Dschietzig T. Relaxin is a candidate drug for lung preservation: relaxin-induced protection of rat lungs from ischemia-reperfusion injury. J Heart Lung Transplant. 2010;29:454-60 pubmed publisher
  23. Boztug K, Klein C. Novel genetic etiologies of severe congenital neutropenia. Curr Opin Immunol. 2009;21:472-80 pubmed publisher
    ..Despite our increasing knowledge of the genetic etiologies of SCN, the molecular pathophysiology underlying these disorders remains only partially understood. ..
  24. Houghton A, Rzymkiewicz D, Ji H, Gregory A, Egea E, Metz H, et al. Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nat Med. 2010;16:219-23 pubmed publisher
    ..Additionally, to our knowledge, this is the first description of a secreted proteinase gaining access to the inside of a cell and altering intracellular signaling. ..
  25. Zynek Litwin M, Kuzniar J, Marchewka Z, Kopec W, Kusztal M, Patrzalek D, et al. Plasma and urine leukocyte elastase-alpha1protease inhibitor complex as a marker of early and long-term kidney graft function. Nephrol Dial Transplant. 2010;25:2346-51 pubmed publisher
    Neutrophils are mediators of ischaemia/reperfusion (I/R) injury following kidney transplantation (kTx). Leukocyte elastase (LE) complex with alpha(1)protease inhibitor (LE-alpha(1)PI) is a marker of neutrophil degranulation...
  26. Wiernicki I, Stachowska E, Safranow K, Cnotliwy M, Rybicka M, Kaczmarczyk M, et al. Enhanced matrix-degrading proteolytic activity within the thin thrombus-covered wall of human abdominal aortic aneurysms. Atherosclerosis. 2010;212:161-5 pubmed publisher
    ..Active MMP-9 concentration did not correlate between sites. The current study demonstrates the differentiation of protease activity within the same AAA wall and its enhancement within the thin thrombus-covered aneurysm wall. ..
  27. Shiohara M, Shigemura T, Saito S, Tanaka M, Yanagisawa R, Sakashita K, et al. Ela2 mutations and clinical manifestations in familial congenital neutropenia. J Pediatr Hematol Oncol. 2009;31:319-24 pubmed publisher
    ..Adults were likely to have less frequent infections than children in familial cases of SCN and CN with the same mutation of Ela2. ..
  28. Lepretre C, Sidoli G, Scovassi A, Torriglia A. Leukocyte elastase inhibitor: a new regulator of PARP-1. Ann N Y Acad Sci. 2009;1171:25-31 pubmed publisher
    ..situation in caspase-independent cell death, we investigated the effect of PARP-1 on the acid endonuclease leukocyte elastase inhibitor (LEI)-derived DNase II (L-DNase II)...
  29. Klein C. Congenital neutropenia. Hematology Am Soc Hematol Educ Program. 2009;:344-50 pubmed publisher
    ..This review addresses diagnostic and therapeutic aspects of congenital neutropenia and covers recent molecular and pathophysiological insights of selected congenital neutropenia syndromes. ..
  30. Paone G, Conti V, Vestri A, Leone A, Puglisi G, Benassi F, et al. Analysis of sputum markers in the evaluation of lung inflammation and functional impairment in symptomatic smokers and COPD patients. Dis Markers. 2011;31:91-100 pubmed publisher
    ..92; for NE 0.81; for IL-8 0.89; for MMP-9 0.81; for HNP, IL-8 and MMP-9 considered together 0.981. The data suggest that the measurement of sputum markers may have an important role in clinical practice for monitoring COPD. ..
  31. Kurtagic E, Jedrychowski M, Nugent M. Neutrophil elastase cleaves VEGF to generate a VEGF fragment with altered activity. Am J Physiol Lung Cell Mol Physiol. 2009;296:L534-46 pubmed publisher
    ..These findings suggest that the tissue response to NE-mediated injury might involve the generation of diffusible VEGF fragments that stimulate inflammatory cell recruitment and activation via VEGF receptor 1. ..
  32. Geraghty P, Rogan M, Greene C, Boxio R, Poiriert T, O Mahony M, et al. Neutrophil elastase up-regulates cathepsin B and matrix metalloprotease-2 expression. J Immunol. 2007;178:5871-8 pubmed
    ..This has important implications for therapeutic intervention in protease-mediated diseases. ..
  33. Ribeiro Gomes F, Moniz de Souza M, Alexandre Moreira M, Dias W, Lopes M, Nunes M, et al. Neutrophils activate macrophages for intracellular killing of Leishmania major through recruitment of TLR4 by neutrophil elastase. J Immunol. 2007;179:3988-94 pubmed
    ..major in draining lymph nodes of TLR4-sufficient, but not TLR4-deficient mice. These results indicate that NE plays a previously unrecognized protective role in host responses to L. major infection. ..
  34. Naylor E, Bakstad D, Biffen M, Thong B, Calverley P, Scott S, et al. Haemophilus influenzae induces neutrophil necrosis: a role in chronic obstructive pulmonary disease?. Am J Respir Cell Mol Biol. 2007;37:135-43 pubmed
    ..However, the infiltrating neutrophils fail to kill the bacteria and instead release tissue-damaging products into the lung as they undergo necrosis. These results may help to explain the clinical picture in COPD. ..
  35. Kodama T, Yukioka H, Kato T, Kato N, Hato F, Kitagawa S. Neutrophil elastase as a predicting factor for development of acute lung injury. Intern Med. 2007;46:699-704 pubmed
    ..The critical level of plasma neutrophil elastase is 220 ng/ml, and the SIRS patients with more than 220 ng/ml neutrophil elastase are highly likely to develop ALI/ARDS. ..
  36. Guyot N, Zani M, Maurel M, Dallet Choisy S, Moreau T. Elafin and its precursor trappin-2 still inhibit neutrophil serine proteinases when they are covalently bound to extracellular matrix proteins by tissue transglutaminase. Biochemistry. 2005;44:15610-8 pubmed
    ..trappin-2 (also called pre-elafin) are potent protein inhibitors of neutrophil serine proteases such as leukocyte elastase and proteinase 3. Trappin-2 has unique conserved sequence motifs rich in Gln and Lys residues...
  37. Köllner I, Sodeik B, Schreek S, Heyn H, von Neuhoff N, Germeshausen M, et al. Mutations in neutrophil elastase causing congenital neutropenia lead to cytoplasmic protein accumulation and induction of the unfolded protein response. Blood. 2006;108:493-500 pubmed
  38. Rescher U, Goebeler V, Wilbers A, Gerke V. Proteolytic cleavage of annexin 1 by human leukocyte elastase. Biochim Biophys Acta. 2006;1763:1320-4 pubmed
    ..resulted in the truncation of annexin 1, which seemed to depend on the proteolytic activity of human leukocyte elastase (HLE)...
  39. Yanagihara K, Fukuda Y, Seki M, Izumikawa K, Miyazaki Y, Hirakata Y, et al. Effects of specific neutrophil elastase inhibitor, sivelestat sodium hydrate, in murine model of severe pneumococcal pneumonia. Exp Lung Res. 2007;33:71-80 pubmed
    ..A possible explanation for the improved survival is that sivelestat prevents tissue damage by inhibiting NE activity in the lung. Therefore, NE inhibitors may be useful for treating with patients with severe pneumonia...
  40. Matsushita H, Asai S, Komiya S, Inoue H, Yabe H, Miyachi H. A family of severe congenital neutropenia with -199C to A substitution in ELA2 promoter. Am J Hematol. 2006;81:985-6 pubmed
  41. Koizumi M, Fujino A, Fukushima K, Kamimura T, Takimoto Kamimura M. Complex of human neutrophil elastase with 1/2SLPI. J Synchrotron Radiat. 2008;15:308-11 pubmed publisher
    ..The mechanisms of the functions of SLPI are relatively unknown, but the current study could help understand the selectivity of SLPI against HNE and PPE. ..
  42. Sethi S, Wrona C, Eschberger K, Lobbins P, Cai X, Murphy T. Inflammatory profile of new bacterial strain exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:491-7 pubmed
    ..Neutrophilic airway inflammation and systemic inflammation are more intense with well-defined bacterial exacerbations than with nonbacterial exacerbations. Clinical course of exacerbation and inflammation are closely linked. ..
  43. Sato T, Takahashi S, Mizumoto T, Harao M, Akizuki M, Takasugi M, et al. Neutrophil elastase and cancer. Surg Oncol. 2006;15:217-22 pubmed
    ..The use of NE inhibitor would seem to be a promising way to prevent the invasion and metastasis of cancer. ..
  44. Hoshi K, Kurosawa S, Kato M, Andoh K, Satoh D, Kaise A. Sivelestat, a neutrophil elastase inhibitor, reduces mortality rate of critically ill patients. Tohoku J Exp Med. 2005;207:143-8 pubmed
    ..3% (7/21) in the untreated group and 6.0% (1/18) in the treated group (p = 0.0236). We conclude that administration of sivelestat reduces mortality of critically ill patients. ..
  45. Suzuki T, Yamashita C, Zemans R, Briones N, Van Linden A, Downey G. Leukocyte elastase induces lung epithelial apoptosis via a PAR-1-, NF-kappaB-, and p53-dependent pathway. Am J Respir Cell Mol Biol. 2009;41:742-55 pubmed publisher
    b>Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability, but the signaling pathways regulating this response remain uncertain...
  46. Hirche T, Benabid R, Deslee G, Gangloff S, Achilefu S, Guenounou M, et al. Neutrophil elastase mediates innate host protection against Pseudomonas aeruginosa. J Immunol. 2008;181:4945-54 pubmed
    ..Consistent with this, the use of an isogenic mutant deficient in outer membrane protein F negated the role of NE in host defense against P. aeruginosa infection...
  47. Horwitz M, Duan Z, Korkmaz B, Lee H, Mealiffe M, Salipante S. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood. 2007;109:1817-24 pubmed
    ..Nevertheless, mutations in all 3 genes are capable of causing the mislocalization of NE and may also induce the unfolded protein response, suggesting that there might a convergent pathogenic mechanism focusing on NE. ..
  48. Donini M, Fontana S, Savoldi G, Vermi W, Tassone L, Gentili F, et al. G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. Blood. 2007;109:4716-23 pubmed
    ..Thereby, we propose that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patients. ..
  49. Nobar S, Zani M, Boudier C, Moreau T, Bieth J. Oxidized elafin and trappin poorly inhibit the elastolytic activity of neutrophil elastase and proteinase 3. FEBS J. 2005;272:5883-93 pubmed
    ..We conclude that in vivo oxidation of elafin and trappin strongly impairs their activity. Inhibitor-based therapy of inflammatory lung diseases must be carried out using oxidation-resistant variants of these molecules. ..
  50. Inoue Y, Seiyama A, Tanaka H, Ukai I, Akimau P, Nishino M, et al. Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on lipopolysaccharide-induced acute dysfunction of the pulmonary microcirculation. Crit Care Med. 2005;33:1814-22 pubmed
    ..The selective neutrophil elastase inhibitor sivelestat reduces neutrophil elastase activity and attenuates acute changes in the pulmonary microcirculation. ..
  51. Griese M, Kappler M, Gaggar A, Hartl D. Inhibition of airway proteases in cystic fibrosis lung disease. Eur Respir J. 2008;32:783-95 pubmed publisher
    ..The present review summarises and discusses the pathophysiological rationales, methodological requirements and clinical implications of inhibition of airway proteases in cystic fibrosis lung disease. ..
  52. Chua F, Dunsmore S, Clingen P, Mutsaers S, Shapiro S, Segal A, et al. Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary fibrosis. Am J Pathol. 2007;170:65-74 pubmed
    ..These data point to novel and unexpected fibrogenic consequences of neutrophil elastase activity in the inflamed lung. ..
  53. Gaggar A, Li Y, Weathington N, Winkler M, Kong M, Jackson P, et al. Matrix metalloprotease-9 dysregulation in lower airway secretions of cystic fibrosis patients. Am J Physiol Lung Cell Mol Physiol. 2007;293:L96-L104 pubmed
    ..Collectively, these findings further emphasize the proposed protease/antiprotease imbalance in chronic neutrophilic lung disease, providing a potential mechanism contributing to this proteolytic dysregulation. ..
  54. Campbell E, Owen C. The sulfate groups of chondroitin sulfate- and heparan sulfate-containing proteoglycans in neutrophil plasma membranes are novel binding sites for human leukocyte elastase and cathepsin G. J Biol Chem. 2007;282:14645-54 pubmed
    Human leukocyte elastase (HLE) and cathepsin G (CG) are expressed at high levels on the surface of activated human neutrophils (PMN) in catalytically active but inhibitor-resistant forms having the potential to contribute to tissue injury...
  55. Stowe A, Adair Kirk T, Gonzales E, Perez R, Shah A, Park T, et al. Neutrophil elastase and neurovascular injury following focal stroke and reperfusion. Neurobiol Dis. 2009;35:82-90 pubmed publisher
  56. Jo Y, Choi H, Jun D, Lee O, Kang J, Park I, et al. The effects of a new human leukocyte elastase inhibitor (recombinant guamerin) on cerulein-induced pancreatitis in rats. Int Immunopharmacol. 2008;8:959-66 pubmed publisher
    ..We aimed to investigate the effects and the possible mechanism of a new human leukocyte elastase inhibitor (recombinant guamerin) in the treatment of cerulein-induced acute pancreatitis in rats...
  57. Hashimoto S, Okayama Y, Shime N, Kimura A, Funakoshi Y, Kawabata K, et al. Neutrophil elastase activity in acute lung injury and respiratory distress syndrome. Respirology. 2008;13:581-4 pubmed publisher
    ..Sivelestat reduced NEA and NEAI in patients with ALI or ARDS suggesting NE inhibition. A larger study is needed to determine the relationship of NEA, NE-AT and NEAI with the outcome of ALI/ARDS. ..
  58. Gando S, Kameue T, Sawamura A, Hayakawa M, Hoshino H, Kubota N. An alternative pathway for fibrinolysis is activated in patients who have undergone cardiopulmonary bypass surgery and major abdominal surgery. Thromb Res. 2007;120:87-93 pubmed
    ..Variations in the correlation coefficients between the levels of elastase-XDP and D-dimer may suggest that elastase-mediated fibrinolysis play a different role from the physiological fibrinolysis mediated by plasmin. ..
  59. Nishiyama T, Yokoyama T, Yamashita K. Effects of a protease inhibitor, ulinastatin, on coagulation and fibrinolysis in abdominal surgery. J Anesth. 2006;20:179-82 pubmed
    Ulinastatin is well known to inhibit the activity of polymorphonuclear leukocyte elastase (PMNE). The PMNE concentration correlates with the activities of coagulation and fibrinolysis...
  60. Liu D, Kao S, Chen H. N-acetylcysteine attenuates acute lung injury induced by fat embolism. Crit Care Med. 2008;36:565-71 pubmed publisher
    ..Posttreatment with NAC abrogated these changes induced by FE. FE caused acute lung injury and associated biochemical changes. Posttreatment with NAC was effective to alleviate the pathologic and biochemical changes caused by FE. ..
  61. Kuwahara I, Lillehoj E, Lu W, Singh I, Isohama Y, Miyata T, et al. Neutrophil elastase induces IL-8 gene transcription and protein release through p38/NF-{kappa}B activation via EGFR transactivation in a lung epithelial cell line. Am J Physiol Lung Cell Mol Physiol. 2006;291:L407-16 pubmed
    ..We conclude that NE increases IL-8 transcription through p38/NF-kappaB activation via EGFR transactivation. ..
  62. Korkmaz B, Moreau T, Gauthier F. Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions. Biochimie. 2008;90:227-42 pubmed
    ..This review focuses on the structural and functional properties of these proteases that may explain their specific biological roles, and facilitate their use as molecular targets for new therapeutic strategies. ..
  63. Fitch P, Roghanian A, Howie S, Sallenave J. Human neutrophil elastase inhibitors in innate and adaptive immunity. Biochem Soc Trans. 2006;34:279-82 pubmed
  64. Steinberg J, Halter J, Schiller H, Gatto L, Carney D, Lee H, et al. Chemically modified tetracycline prevents the development of septic shock and acute respiratory distress syndrome in a clinically applicable porcine model. Shock. 2005;24:348-56 pubmed
  65. Karlsson J, Carlsson G, Ramme K, Hagglund H, Fadeel B, Nordenskjold M, et al. Low plasma levels of the protein pro-LL-37 as an early indication of severe disease in patients with chronic neutropenia. Br J Haematol. 2007;137:166-9 pubmed
    ..Plasma levels of pro-LL-37 may thus prove useful for differential diagnosis of chronic neutropenia. ..
  66. Grenda D, Murakami M, Ghatak J, Xia J, Boxer L, Dale D, et al. Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. Blood. 2007;110:4179-87 pubmed
    ..Collectively, these data provide strong support for a UPR model of SCN disease pathogenesis and place SCN in a growing list of human diseases caused by misfolded proteins. ..
  67. Ilumets H, Rytilä P, Sovijärvi A, Tervahartiala T, Myllärniemi M, Sorsa T, et al. Transient elevation of neutrophil proteinases in induced sputum during COPD exacerbation. Scand J Clin Lab Invest. 2008;68:618-23 pubmed publisher