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Gene Review

Elane  -  elastase, neutrophil expressed

Mus musculus

Synonyms: Ela2, Elastase-2, F430011M15Rik, Leukocyte elastase, NE, ...
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Disease relevance of Ela2


High impact information on Ela2

  • Excess NE produces lesions in GB -/- mice without cleaving alpha1-PI [1].
  • Only NE degrades BP180 and produces dermal-epidermal separation in vivo and in culture [1].
  • In neutrophils, NE is stored in azurophil granules along with other serine proteinases (cathepsin G, proteinase 3 and azurocidin) at concentrations exceeding 5 mM [2].
  • As a result of its capacity to efficiently degrade extracellular matrix, NE has been implicated in a variety of destructive diseases [2].
  • Elastase release in the inflamed tissue was reduced in Mac-1-deficient mice, and a deficiency of Mac-1 or the kinases blocked neutrophil elastase release in vitro [4].

Chemical compound and disease context of Ela2


Biological context of Ela2

  • Recent studies have demonstrated that the majority of patients with SCN and cyclic neutropenia, a related disorder characterized by periodic oscillations in the number of circulating neutrophils, have heterozygous germline mutations in the ELA2 gene encoding neutrophil elastase (NE) [3].
  • Collectively, these data suggest that expression of V72M NE is not sufficient to induce an SCN phenotype or leukemia in mice [3].
  • Furthermore, phagocytosis of fluorescent zymosan particles, as observed by intravital microscopy, was diminished in NE-deficient animals [9].
  • Deletional analysis of the enhancer identified several segments which activated the neutrophil elastase and thymidine kinase promoters 3-6-fold [10].
  • In this study we found that macrophage metalloelastase, MMP-12 cleaves, in vitro, apolipoprotein(a) (apo(a)) in the Asn3518-Val3519 bond located in the linker region between kringles IV-4 and IV-5, a bond immediately upstream of the Ile3520-Leu3521 bond, shown previously to be the site of action by neutrophil elastase (NE) [11].

Anatomical context of Ela2

  • The myeloperoxidase (MPO) and neutrophil elastase genes are expressed specifically in immature myeloid cells [12].
  • Cigarette smoke-induced recruitment of both neutrophils and monocytes was impaired in the absence of neutrophil elastase [13].
  • Collectively, the findings suggest that, whereas regulation of the expression of alpha6 integrins and NE occur via different adhesive mechanisms, these molecules might act in a cooperative manner in mediating neutrophil migration through venular walls, in particular the perivascular basement membrane [14].
  • In this context, blockade of alpha6 integrins (laminin receptors), neutrophil elastase (NE) or both inhibited neutrophil migration through interleukin-1beta (IL-1beta)-stimulated mouse cremasteric venules, as observed by intravital microscopy [14].
  • Collectively, the findings of this study indicate a nonredundant role for NE in zymosan-induced leukocyte firm adhesion and transmigration, and that this defect is associated with impaired generation of proinflammatory mediators as well as phagocytosis of zymosan particles in vivo [9].

Associations of Ela2 with chemical compounds

  • In order to assess the protease-dependence of the BLM-induced lesion, a group mice was treated with 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride, a serine proteinase inhibitor active toward neutrophil elastase [15].
  • 3. NE and EO recruitment induced by dead mycelial form of fungus (DMH) was greater than that observed for dead yeast form of fungus (DYH) [16].
  • However, other mediators appear to contribute to NE and EO migration since the treatment with Dexa was more effective in inhibiting cell migration than MK886 [16].
  • The activity of this streptococcal binding receptor was inhibited by 2-deoxy-D-glucose but not by neutrophil elastase [17].

Regulatory relationships of Ela2


Other interactions of Ela2

  • This protective effect correlates with the inactivation of neutrophil-derived serine proteases, since NE(-/-) x CG(-/-) mice are equally resistant to arthritis induction by anti-collagen antibodies [21].
  • These results suggest that Stat6-protease may belong to the elastase family but differs from NE or PR3 [22].
  • Moreover, there was less macrophage elastase activity secondary to decreased macrophage accumulation in neutrophil elastase-deficient mice [13].
  • Despite different regulatory mechanisms, blockade of alpha6 integrins or NE inhibited migration of murine neutrophils through laminin-coated filters in vitro [14].
  • Two hereditary human leukemia syndromes are severe congenital neutropenia (SCN), caused by mutations in the gene ELA2, encoding the protease neutrophil elastase, and familial platelet disorder with acute myelogenous leukemia (AML), caused by mutations in the gene AML1, encoding the transcription factor core-binding factor alpha (CBFalpha) [23].

Analytical, diagnostic and therapeutic context of Ela2


  1. The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo. Liu, Z., Zhou, X., Shapiro, S.D., Shipley, J.M., Twining, S.S., Diaz, L.A., Senior, R.M., Werb, Z. Cell (2000) [Pubmed]
  2. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Belaaouaj, A., McCarthy, R., Baumann, M., Gao, Z., Ley, T.J., Abraham, S.N., Shapiro, S.D. Nat. Med. (1998) [Pubmed]
  3. Mice expressing a neutrophil elastase mutation derived from patients with severe congenital neutropenia have normal granulopoiesis. Grenda, D.S., Johnson, S.E., Mayer, J.R., McLemore, M.L., Benson, K.F., Horwitz, M., Link, D.C. Blood (2002) [Pubmed]
  4. Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Hirahashi, J., Mekala, D., Van Ziffle, J., Xiao, L., Saffaripour, S., Wagner, D.D., Shapiro, S.D., Lowell, C., Mayadas, T.N. Immunity (2006) [Pubmed]
  5. Effects of neutrophil elastase inhibitor on bleomycin-induced pulmonary fibrosis in mice. Taooka, Y., Maeda, A., Hiyama, K., Ishioka, S., Yamakido, M. Am. J. Respir. Crit. Care Med. (1997) [Pubmed]
  6. Deficiency in neutrophil elastase does not impair neutrophil recruitment to inflamed sites. Hirche, T.O., Atkinson, J.J., Bahr, S., Belaaouaj, A. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  7. Proteases and emphysema. Churg, A., Wright, J.L. Current opinion in pulmonary medicine. (2005) [Pubmed]
  8. Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis. Morohoshi, Y., Matsuoka, K., Chinen, H., Kamada, N., Sato, T., Hisamatsu, T., Okamoto, S., Inoue, N., Takaishi, H., Ogata, H., Iwao, Y., Hibi, T. J. Gastroenterol. (2006) [Pubmed]
  9. Neutrophil elastase (NE)-deficient mice demonstrate a nonredundant role for NE in neutrophil migration, generation of proinflammatory mediators, and phagocytosis in response to zymosan particles in vivo. Young, R.E., Thompson, R.D., Larbi, K.Y., La, M., Roberts, C.E., Shapiro, S.D., Perretti, M., Nourshargh, S. J. Immunol. (2004) [Pubmed]
  10. An enhancer located between the neutrophil elastase and proteinase 3 promoters is activated by Sp1 and an Ets factor. Nuchprayoon, I., Shang, J., Simkevich, C.P., Luo, M., Rosmarin, A.G., Friedman, A.D. J. Biol. Chem. (1999) [Pubmed]
  11. Macrophage metalloelastase, MMP-12, cleaves human apolipoprotein(a) in the linker region between kringles IV-4 and IV-5. Potential relevance to lipoprotein(a) biology. Edelstein, C., Shapiro, S.D., Klezovitch, O., Scanu, A.M. J. Biol. Chem. (1999) [Pubmed]
  12. PEBP2/CBF, the murine homolog of the human myeloid AML1 and PEBP2 beta/CBF beta proto-oncoproteins, regulates the murine myeloperoxidase and neutrophil elastase genes in immature myeloid cells. Nuchprayoon, I., Meyers, S., Scott, L.M., Suzow, J., Hiebert, S., Friedman, A.D. Mol. Cell. Biol. (1994) [Pubmed]
  13. Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Shapiro, S.D., Goldstein, N.M., Houghton, A.M., Kobayashi, D.K., Kelley, D., Belaaouaj, A. Am. J. Pathol. (2003) [Pubmed]
  14. PECAM-1, alpha6 integrins and neutrophil elastase cooperate in mediating neutrophil transmigration. Wang, S., Dangerfield, J.P., Young, R.E., Nourshargh, S. J. Cell. Sci. (2005) [Pubmed]
  15. Is neutrophil elastase the missing link between emphysema and fibrosis? Evidence from two mouse models. Lucattelli, M., Bartalesi, B., Cavarra, E., Fineschi, S., Lunghi, B., Martorana, P.A., Lungarella, G. Respir. Res. (2005) [Pubmed]
  16. Leukotrienes are involved in leukocyte recruitment induced by live Histoplasma capsulatum or by the beta-glucan present in their cell wall. Medeiros, A.I., Silva, C.L., Malheiro, A., Maffei, C.M., Faccioli, L.H. Br. J. Pharmacol. (1999) [Pubmed]
  17. Characterization of the murine macrophage receptor for group B streptococci. Sloan, A.R., Pistole, T.G. Zentralbl. Bakteriol. (1993) [Pubmed]
  18. C/EBP, c-Myb, and PU.1 cooperate to regulate the neutrophil elastase promoter. Oelgeschläger, M., Nuchprayoon, I., Lüscher, B., Friedman, A.D. Mol. Cell. Biol. (1996) [Pubmed]
  19. Production and pharmacologic modulation of the granulocyte-associated allergic responses to ovalbumin in murine skin models induced by injecting ovalbumin-specific Th1 or Th2 cells. Terui, T., Sano, K., Okada, M., Shirota, H., Honda, M., Ozawa, M., Hirasawa, N., Tamura, G., Tagami, H. J. Invest. Dermatol. (2001) [Pubmed]
  20. Neutrophil elastase enhances macrophage production of chemokines in receptor-mediated reaction. Ishihara, K., Yamaguchi, Y., Okabe, K., Ogawa, M. Res. Commun. Mol. Pathol. Pharmacol. (1999) [Pubmed]
  21. Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis. Adkison, A.M., Raptis, S.Z., Kelley, D.G., Pham, C.T. J. Clin. Invest. (2002) [Pubmed]
  22. Stat6-protease but not Stat5-protease is inhibited by an elastase inhibitor ONO-5046. Suzuki, K., Nakajima, H., Ikeda, K., Tamachi, T., Hiwasa, T., Saito, Y., Iwamoto, I. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  23. Lymphoid enhancer factor-1 links two hereditary leukemia syndromes through core-binding factor alpha regulation of ELA2. Li, F.Q., Person, R.E., Takemaru, K., Williams, K., Meade-White, K., Ozsahin, A.H., Güngör, T., Moon, R.T., Horwitz, M. J. Biol. Chem. (2004) [Pubmed]
  24. Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary fibrosis. Chua, F., Dunsmore, S.E., Clingen, P.H., Mutsaers, S.E., Shapiro, S.D., Segal, A.W., Roes, J., Laurent, G.J. Am. J. Pathol. (2007) [Pubmed]
  25. Involvement of a serine protease, but not of neutrophil elastase, in tumor necrosis factor-induced lethal hepatitis and induction of platelet-activating factor. Wielockx, B., Bussolino, F., Shapiro, S.D., Libert, C. J. Hepatol. (2001) [Pubmed]
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