Startseite Proteolytic susceptibility of the serine protease inhibitor trappin-2 (pre-elafin): evidence for tryptase-mediated generation of elafin
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Proteolytic susceptibility of the serine protease inhibitor trappin-2 (pre-elafin): evidence for tryptase-mediated generation of elafin

  • Nicolas Guyot , Marie-Louise Zani , Patrick Berger , Sandrine Dallet-Choisy und Thierry Moreau
Veröffentlicht/Copyright: 5. Juli 2005
Biological Chemistry
Aus der Zeitschrift Band 386 Heft 4

Abstract

A number of serine, cysteine, metallo- and acid proteases were evaluated for their ability to proteolytically cleave the serine protease inhibitor trappin-2, also known as pre-elafin, and to release elafin from its precursor. None of the metalloproteases or acid proteases examined cleaved trappin-2, while serine and cysteine proteases preferentially cleaved trappin-2 within its non-inhibitory N-terminal moiety. Cathepsin L, cathepsin K, plasmin, trypsin and tryptase were able to release elafin by cleaving the Lys38-Ala39 peptide bond in trappin-2. However, purified tryptase appeared to be efficient at releasing elafin. Incubation of trappin-2 with purified mast cells first challenged with anti-immunoglobulin E or calcium ionophore A23187 resulted in the rapid generation of elafin. This proteolytic release of elafin from trappin-2 was inhibited in the presence of a tryptase inhibitor, suggesting that this mast cell enzyme was involved in the process. Finally, ex vivo incubation of trappin-2 with sputum from cystic fibrosis patients indicated the production of a proteolytic immunoreactive fragment with the same mass as that of native elafin. This cleavage did not occur when preincubating the sputum with polyclonal antibodies directed against tryptase. Taken together, these findings indicate that tryptase could likely be involved in the maturation of trappin-2 into elafin under physiological conditions.

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References

Bairoch, A., Bucher, P., and Hofmann, K. (1997). The PROSITE database, its status in 1997. Nucleic Acids Res.25, 217–221.10.1093/nar/25.1.217Suche in Google Scholar

Berger, P., Perng, D.W., Thabrew, H., Compton, S.J., Cairns, J.A., McEuen, A.R., Marthan, R., Tunon De Lara, J.M., and Walls, A.F. (2001). Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells. J. Appl. Physiol.91, 1372–1379.10.1152/jappl.2001.91.3.1372Suche in Google Scholar

Berger, P., Girodet, P.O., Begueret, H., Ousova, O., Perng, D.W., Marthan, R., Walls, A.F., and Tunon de Lara, J.M. (2003). Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis. FASEB J.17, 2139–2141.10.1096/fj.03-0041fjeSuche in Google Scholar

Coleman, P.L., Lathham, H.G. Jr., and Shaw, E.N. (1976). Some sensitive methods for the assay of trypsin-like enzymes. Methods Enzymol.45, 12–26.10.1016/S0076-6879(76)45004-8Suche in Google Scholar

Delacourt, C., Herigault, S., Delclaux, C., Poncin, A., Levame, M., Harf, A., Saudubray, F., and Lafuma, C. (2002). Protection against acute lung injury by intravenous or intratracheal pretreatment with EPI-HNE-4, a new potent neutrophil elastase inhibitor. Am. J. Respir. Cell. Mol. Biol.26, 290–297.10.1165/ajrcmb.26.3.4611Suche in Google Scholar

Duffy, M.S., Berger, P., Cruse, G., Yang, W., Bolton, S.J., and Bradding, P. (2004). The K+ channel iKCA1 potentiates Ca2+ influx and degranulation in human lung mast cells. J. Allergy Clin. Immunol.114, 66–72.10.1016/j.jaci.2004.04.005Suche in Google Scholar

Fiorucci, L. and Ascoli, F. (2004). Mast cell tryptase, a still enigmatic enzyme. Cell. Mol. Life Sci.61, 1278–1295.10.1007/s00018-004-3400-0Suche in Google Scholar

Henriksen, P.A., Hitt, M., Xing, Z., Wang, J., Haslett, C., Riemersma, R.A., Webb, D.J., Kotelevtsev, Y.V., and Sallenave, J.M. (2004). Adenoviral gene delivery of elafin and secretory leukocyte protease inhibitor attenuates NF-κB-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. J. Immunol.172, 4535–4544.10.4049/jimmunol.172.7.4535Suche in Google Scholar

King, A.E., Critchley, H.O., Sallenave, J.M., and Kelly, R.W. (2003). Elafin in human endometrium: an antiprotease and antimicrobial molecule expressed during menstruation. J. Clin. Endocrinol. Metab.88, 4426–4431.10.1210/jc.2003-030239Suche in Google Scholar

Laskowski, M. and Qasim, M.A. (2000). What can the structures of enzyme-inhibitor complexes tell us about the structures of enzyme substrate complexes? Biochim. Biophys. Acta1477, 324–337.Suche in Google Scholar

Marquardt, U., Zettl, F., Huber, R., Bode, W., and Sommerhoff, C. (2002). The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region. J. Mol. Biol.321, 491–502.10.1016/S0022-2836(02)00625-3Suche in Google Scholar

McElvaney, N.G., Hubbard, R.C., Birrer, P., Chernick, M.S., Caplan, D.B., Frank, M.M., and Crystal, R.G. (1991). Aerosol α1-antitrypsin treatment for cystic fibrosis. Lancet337, 392–394.10.1016/0140-6736(91)91167-SSuche in Google Scholar

Mihaila, A. and Tremblay, G.M. (2001). Human alveolar macrophages express elafin and secretory leukocyte protease inhibitor. Z. Naturforsch.56, 291–297.10.1515/znc-2001-3-420Suche in Google Scholar

Molhuizen, H.O., Alkemade, H.A., Zeeuwen, P.L., de Jongh, G.J., Wieringa, B., and Schalkwijk, J. (1993). SKALP/elafin: an elastase inhibitor from cultured human keratinocytes. Purification, cDNA sequence, and evidence for transglutaminase cross-linking. J. Biol. Chem.268, 12028–12032.Suche in Google Scholar

Nakane, H., Ishida-Yamamoto, A., Takahashi, H., and Iizuka, H. (2002). Elafin, a secretory protein, is cross-linked into the cornified cell envelopes from the inside of psoriatic keratinocytes. J. Invest. Dermatol.119, 50–55.10.1046/j.1523-1747.2002.01803.xSuche in Google Scholar

Nara, K., Ito, S., Ito, T., Suzuki, Y., Ghoneim, M.A., Tachibana, S., and Hirose, S. (1994). Elastase inhibitor elafin is a new type of proteinase inhibitor which has a transglutaminase-mediated anchoring sequence termed ‘cementoin’. J. Biochem.115, 441–448.10.1093/oxfordjournals.jbchem.a124357Suche in Google Scholar

Owen, C.A. and Campbell, E.J. (1999). The cell biology of leukocyte-mediated proteolysis. J. Leukoc. Biol.65, 137–150.10.1002/jlb.65.2.137Suche in Google Scholar

Peng, Q., McEuen, A.R., Benyon, R.C., and Walls, A.F. (2003). The heterogeneity of mast cell tryptase from human lung and skin. Eur. J. Biochem.270, 270–283.10.1046/j.1432-1033.2003.03385.xSuche in Google Scholar

Pfundt, R., van Ruissen, F., van Vlijmen-Willems, I.M., Alkemade, H.A., Zeeuwen, P.L., Jap, P.H., Dijkman, H., Fransen, J., Croes, H., van Erp, P.E., and Schalkwijk, J. (1996). Constitutive and inducible expression of SKALP/elafin provides anti-elastase defense in human epithelia. J. Clin. Invest.98, 1389–1399.10.1172/JCI118926Suche in Google Scholar

Saheki, T., Ito, F., Hagiwara, H., Saito, Y., Kuroki, J., Tachibana, S., and Hirose, S. (1992). Primary structure of the human elafin precursor preproelafin deduced from the nucleotide sequence of its gene and the presence of unique repetitive sequences in the prosegment. Biochem. Biophys. Res. Commun.185, 240–245.10.1016/S0006-291X(05)80981-7Suche in Google Scholar

Sallenave, J.M. and Ryle, A.P. (1991). Purification and characterization of elastase-specific inhibitor. Sequence homology with mucus proteinase inhibitor. Biol. Chem. Hoppe-Seyler372, 13–21.Suche in Google Scholar

Sallenave, J.M. and Silva, A. (1993). Characterization and gene sequence of the precursor of elafin, an elastase-specific inhibitor in bronchial secretions. Am. J. Respir. Cell. Mol. Biol.8, 439–445.10.1165/ajrcmb/8.4.439Suche in Google Scholar PubMed

Sallenave, J.M., Marsden, M.D., and Ryle, A.P. (1992). Isolation of elafin and elastase-specific inhibitor (ESI) from bronchial secretions. Evidence of sequence homology and immunological cross-reactivity. Biol. Chem. Hoppe-Seyler373, 27–33.Suche in Google Scholar

Sallenave, J.M., Silva, A., Marsden, M.E., and Ryle, A.P. (1993). Secretion of mucus proteinase inhibitor and elafin by Clara cell and type II pneumocyte cell lines. Am. J. Respir. Cell. Mol. Biol.8, 126–133.10.1165/ajrcmb/8.2.126Suche in Google Scholar PubMed

Sallenave, J.M., Shulmann, J., Crossley, J., Jordana, M., and Gauldie, J. (1994). Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Am. J. Respir. Cell. Mol. Biol.11, 733–741.10.1165/ajrcmb.11.6.7946401Suche in Google Scholar

Sallenave, J.M., Xing, Z., Graham, F., and Gauldie, J. (1997). In vivo adenovirus-mediated expression of human pre-elafin, a potent neutrophil elastase inhibitor. Chest111, 128S–129S.10.1378/chest.111.6_Supplement.128SSuche in Google Scholar

Schägger, H. and von Jagow, G. (1987). Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal. Biochem.166, 368–379.10.1016/0003-2697(87)90587-2Suche in Google Scholar

Schalkwijk, J., Chang, A., Janssen, P., De Jongh, G.J., and Mier, P.D. (1990). Skin-derived antileucoproteases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis. Br. J. Dermatol.122, 631–641.10.1111/j.1365-2133.1990.tb07285.xSuche in Google Scholar

Schalkwijk, J., Wiedow, O., and Hirose, S. (1999). The trappin gene family: proteins defined by an N-terminal transglutaminase substrate domain and a C-terminal four-disulphide core. Biochem. J.340, 569–577.10.1042/bj3400569Suche in Google Scholar

Simpson, A.J., Maxwell, A.I., Govan, J.R., Haslett, C., and Sallenave, J.M. (1999). Elafin (elastase-specific inhibitor) has anti-microbial activity against Gram-positive and Gram-negative respiratory pathogens. FEBS Lett.452, 309–313.10.1016/S0014-5793(99)00670-5Suche in Google Scholar

Steinert, P.M. and Marekov, L.N. (1995). The proteins elafin, filaggrin, keratin intermediate filaments, loricrin, and small proline-rich proteins 1 and 2 are isodipeptide cross-linked components of the human epidermal cornified cell envelope. J. Biol. Chem.270, 17702–17711.10.1074/jbc.270.30.17702Suche in Google Scholar

Taggart, C.C., Greene, C.M., Smith, S.G., Levine, R.L., McCray, P.B. Jr., O'Neill, S., and McElvaney, N.G. (2003). Inactivation of human β-defensins 2 and 3 by elastolytic cathepsins. J. Immunol.171, 931–937.10.4049/jimmunol.171.2.931Suche in Google Scholar

Thompson, K. and Rabinovitch, M. (1996). Exogenous leukocyte and endogenous elastases can mediate mitogenic activity in pulmonary artery smooth muscle cells by release of extracellular-matrix bound basic fibroblast growth factor. J. Cell. Physiol.166, 495–505.10.1002/(SICI)1097-4652(199603)166:3<495::AID-JCP4>3.0.CO;2-KSuche in Google Scholar

Tremblay, G.M., Sallenave, J.M., Israel-Assayag, E., Cormier, Y., and Gauldie, J. (1996). Elafin/elastase-specific inhibitor in bronchoalveolar lavage of normal subjects and farmer's lung. Am. J. Respir. Crit. Care Med.154, 1092–1098.10.1164/ajrccm.154.4.8887613Suche in Google Scholar

Tremblay, G.M., Vachon, E., Larouche, C., and Bourbonnais, Y. (2002). Inhibition of human neutrophil elastase-induced acute lung injury in hamsters by recombinant human pre-elafin (trappin-2). Chest121, 582–588.10.1378/chest.121.2.582Suche in Google Scholar

Tremblay, G.M., Janelle, M.F., and Bourbonnais, Y. (2003). Anti-inflammatory activity of neutrophil elastase inhibitors. Curr. Opin. Invest. Drugs4, 556–565.Suche in Google Scholar

Vogelmeier, C., Gillissen, A., and Buhl, R. (1996). Use of secretory leukoprotease inhibitor to augment lung antineutrophil elastase activity. Chest110, 261S–266S.10.1378/chest.110.6_Supplement.261SSuche in Google Scholar

Walls, A.F., Bennett, A.R., Godfrey, R.C., Holgate, S.T., and Church, M.K. (1991). Mast cell tryptase and histamine concentrations in bronchoalveolar lavage fluid from patients with interstitial lung disease. Clin. Sci.81, 183–188.10.1042/cs0810183Suche in Google Scholar

Wiedow, O., Schroder, J.M., Gregory, H., Young, J.A., and Christophers, E. (1990). Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence. J. Biol. Chem.265, 14791–14795.Suche in Google Scholar

Zani, M.L., Brillard-Bourdet, M., Lazure, C., Juliano, L., Courty, Y., Gauthier, F., and Moreau, T. (2001). Purification and characterization of active recombinant rat kallikrein rK9. Biochim. Biophys. Acta1547, 387–396.10.1016/S0167-4838(01)00208-4Suche in Google Scholar

Zani, M.L., Nobar, S.M., Lacour, S.A., Lemoine, S., Boudier, C., Bieth, J.G., and Moreau, T. (2004). Kinetics of the inhibition of neutrophil proteinases by recombinant elafin and pre-elafin (trappin-2) expressed in Pichia pastoris. Eur. J. Biochem.271, 2370–2378.10.1111/j.1432-1033.2004.04156.xSuche in Google Scholar PubMed

Zeeuwen, P.L., Hendriks, W., de Jong, W.W., and Schalkwijk, J. (1997). Identification and sequence analysis of two new members of the SKALP/elafin and SPAI-2 gene family. Biochemical properties of the transglutaminase substrate motif and suggestions for a new nomenclature. J. Biol. Chem.272, 20471–20478.10.1074/jbc.272.33.20471Suche in Google Scholar PubMed

Published Online: 2005-07-05
Published in Print: 2005-04-01

© by Walter de Gruyter Berlin New York

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