Skip to main content
Erschienen in: Intensive Care Medicine 12/2009

01.12.2009 | Pediatric Original

Bronchoalveolar lavage fluid peptidomics suggests a possible matrix metalloproteinase-3 role in bronchopulmonary dysplasia

verfasst von: Giovanni Vento, Chiara Tirone, Paola Lulli, Ettore Capoluongo, Franco Ameglio, Simona Lozzi, Francesco Cota, Fabio Mosca, Costantino Romagnoli, Irene Messana, Massimo Castagnola, Rosanna Inzitari

Erschienen in: Intensive Care Medicine | Ausgabe 12/2009

Einloggen, um Zugang zu erhalten

Abstract

Background

Bronchoalveolar lavage fluid (BALF) is an important diagnostic source to investigate molecular changes occurring in lung disorders. The objective of this study was to assess and compare the peptidomic profiles of BALF from premature neonates with and without bronchopulmonary dysplasia (BPD).

Methods

Samples were obtained on the 3rd day of life from 34 neonates with gestational age ≤32 weeks. Two pools of samples from patients with and without BPD were analyzed by high performance liquid chromatography. Several differentially expressed peptides were collected and sequenced. Moreover, samples from single donors were analyzed by liquid chromatography-electrospray ionization mass spectrometry to define the molecular mass values of various peptides and to quantify their expression. Levels of some matrix metalloproteinases and their tissue inhibitors were also determined in single samples.

Results

Neonates of the BPD group (N = 16) showed significantly lower mean gestational age and birth weight with respect to the no-BPD group (N = 18; P < 0.0001). Levels of six peptides were significantly higher in BPD patients (P < 0.05). Two of them were identified as the albumin fragments 1–21 (2,428 Da) and 399–406 (956 Da). Levels of matrix metalloproteinase-3 (MMP-3) enzyme probably involved in albumin fragment generation were also significantly higher in the BPD group compared to the no-BPD group (P < 0.05), whereas the levels of tissue inhibitor of metalloproteinases-1 were significantly lower (P < 0.05). Levels of albumin fragments and MMP-3 showed a significant correlation (P < 0.05).

Conclusions

This study shows that proteomic techniques can be applied to investigate the involvement of proteolytic enzymes on the airways of mechanically ventilated premature infants.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Waittiez R, Falmagne P (2005) Proteomics of bronchoalveolar lavage fluid. J Chromatogr B Analyt Technol Biomed Life Sci 815:169–178CrossRef Waittiez R, Falmagne P (2005) Proteomics of bronchoalveolar lavage fluid. J Chromatogr B Analyt Technol Biomed Life Sci 815:169–178CrossRef
2.
Zurück zum Zitat Bowler RP, Duda B, Chan ED, Enghild JJ, Ware LB, Matthay MA, Duncan MW (2004) Proteomic analysis of pulmonary edema fluid and plasma in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol 286:L1095–L1104CrossRefPubMed Bowler RP, Duda B, Chan ED, Enghild JJ, Ware LB, Matthay MA, Duncan MW (2004) Proteomic analysis of pulmonary edema fluid and plasma in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol 286:L1095–L1104CrossRefPubMed
3.
Zurück zum Zitat Hirsch J, Hansen KC, Burlingame AL, Matthay MA (2004) Proteomics: current techniques and potential applications to lung disease. Am J Physiol Lung Cell Mol Physiol 287:L1–L23CrossRefPubMed Hirsch J, Hansen KC, Burlingame AL, Matthay MA (2004) Proteomics: current techniques and potential applications to lung disease. Am J Physiol Lung Cell Mol Physiol 287:L1–L23CrossRefPubMed
4.
Zurück zum Zitat Waittiez R, Hermans C, Bernard A, Lesur O, Falmagne P (1999) Human bronchoalveolar lavage fluid: two-dimensional gel electrophoresis, amino acid microsequencing and identification of major proteins. Electrophoresis 20:1634–1645CrossRef Waittiez R, Hermans C, Bernard A, Lesur O, Falmagne P (1999) Human bronchoalveolar lavage fluid: two-dimensional gel electrophoresis, amino acid microsequencing and identification of major proteins. Electrophoresis 20:1634–1645CrossRef
5.
Zurück zum Zitat Waittiez R, Hermans C, Cruyt C, Bernard A, Falmagne P (2000) Human bronchoalveolar lavage fluid protein two dimensional database: study of interstitial lung diseases. Electrophoresis 21:2703–2712CrossRef Waittiez R, Hermans C, Cruyt C, Bernard A, Falmagne P (2000) Human bronchoalveolar lavage fluid protein two dimensional database: study of interstitial lung diseases. Electrophoresis 21:2703–2712CrossRef
6.
Zurück zum Zitat Fietta AM, Bardoni AM, Salvini R, Passadore I, Morosini M, Cavagna L, Codullo V, Pozzi E, Meloni F, Montecucco C (2006) Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis. Arthritis Res Ther 8:R160CrossRefPubMed Fietta AM, Bardoni AM, Salvini R, Passadore I, Morosini M, Cavagna L, Codullo V, Pozzi E, Meloni F, Montecucco C (2006) Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis. Arthritis Res Ther 8:R160CrossRefPubMed
7.
Zurück zum Zitat Noël-Georis I, Bernard A, Falmagne P, Wattiez R (2001) Proteomics as the tool to search for lung disease markers in bronchoalveolar lavage. Dis Markers 17:271–284PubMed Noël-Georis I, Bernard A, Falmagne P, Wattiez R (2001) Proteomics as the tool to search for lung disease markers in bronchoalveolar lavage. Dis Markers 17:271–284PubMed
8.
Zurück zum Zitat Plymoth A, Löfdahl CG, Ekberg-Jansson A, Dahlbäck M, Broberg P, Foster M, Fehniger TE, Marko-Varga G (2007) Protein expression patterns associated with progression of chronic obstructive pulmonary disease in bronchoalveolar lavage of smokers. Clin Chem 53:636–644CrossRefPubMed Plymoth A, Löfdahl CG, Ekberg-Jansson A, Dahlbäck M, Broberg P, Foster M, Fehniger TE, Marko-Varga G (2007) Protein expression patterns associated with progression of chronic obstructive pulmonary disease in bronchoalveolar lavage of smokers. Clin Chem 53:636–644CrossRefPubMed
9.
Zurück zum Zitat Lenz AG, Meyer B, Costabel U, Maier K (1993) Bronchoalveolar lavage fluid proteins in human lung disease: analysis by two-dimensional electrophoresis. Electrophoresis 14:242–244CrossRefPubMed Lenz AG, Meyer B, Costabel U, Maier K (1993) Bronchoalveolar lavage fluid proteins in human lung disease: analysis by two-dimensional electrophoresis. Electrophoresis 14:242–244CrossRefPubMed
10.
Zurück zum Zitat Lindahl M, Ståhlbom B, Tagesson C (1995) Two-dimensional gel electrophoresis of nasal and bronchoalveolar lavage fluids after occupational exposure. Electrophoresis 16:1199–1204CrossRefPubMed Lindahl M, Ståhlbom B, Tagesson C (1995) Two-dimensional gel electrophoresis of nasal and bronchoalveolar lavage fluids after occupational exposure. Electrophoresis 16:1199–1204CrossRefPubMed
11.
Zurück zum Zitat Lindahl M, Ståhlbom B, Tagesson C (1999) Newly identified proteins in human nasal and bronchoalveolar lavage fluids: potential biomedical and clinical applications. Electrophoresis 20:3670–3676CrossRefPubMed Lindahl M, Ståhlbom B, Tagesson C (1999) Newly identified proteins in human nasal and bronchoalveolar lavage fluids: potential biomedical and clinical applications. Electrophoresis 20:3670–3676CrossRefPubMed
12.
Zurück zum Zitat Magi B, Bini L, Perari MG, Fossi A, Sanchez JC, Hochstrasser D, Paesano S, Raggiaschi R, Santucci A, Pallini V, Rottoli P (2002) Bronchoalveolar lavage fluid protein composition in patients with sarcoidosis and idiopathic pulmonary fibrosis: a two-dimensional electrophoretic study. Electrophoresis 23:3434–3444CrossRefPubMed Magi B, Bini L, Perari MG, Fossi A, Sanchez JC, Hochstrasser D, Paesano S, Raggiaschi R, Santucci A, Pallini V, Rottoli P (2002) Bronchoalveolar lavage fluid protein composition in patients with sarcoidosis and idiopathic pulmonary fibrosis: a two-dimensional electrophoretic study. Electrophoresis 23:3434–3444CrossRefPubMed
13.
Zurück zum Zitat Sabounchi-Schütt F, Aström J, Hellman U, Eklund A, Grunewald J (2003) Changes in bronchoalveolar lavage fluid proteins in sarcoidosis: a proteomics approach. Eur Respir J 21:414–420CrossRefPubMed Sabounchi-Schütt F, Aström J, Hellman U, Eklund A, Grunewald J (2003) Changes in bronchoalveolar lavage fluid proteins in sarcoidosis: a proteomics approach. Eur Respir J 21:414–420CrossRefPubMed
14.
Zurück zum Zitat Ashton MR, Postle AD, Hall MA, Smith SL, Kelly FJ, Normand IC (1992) Phosphatidylcholine composition of endotracheal tube aspirates of neonates and subsequent respiratory disease. Arch Dis Child 67(4 Spec No):378–382CrossRefPubMed Ashton MR, Postle AD, Hall MA, Smith SL, Kelly FJ, Normand IC (1992) Phosphatidylcholine composition of endotracheal tube aspirates of neonates and subsequent respiratory disease. Arch Dis Child 67(4 Spec No):378–382CrossRefPubMed
15.
Zurück zum Zitat Vento G, Matassa PG, Ameglio F, Capoluongo E, Zecca E, Tortorolo L, Martelli M, Romagnoli C (2005) HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Intensive Care Med 31:463–470CrossRefPubMed Vento G, Matassa PG, Ameglio F, Capoluongo E, Zecca E, Tortorolo L, Martelli M, Romagnoli C (2005) HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Intensive Care Med 31:463–470CrossRefPubMed
16.
Zurück zum Zitat Su BH, Watanabe T, Shimizu M, Yanagisawa M (1997) Echocardiographic assessment of patent ductus arteriosus shunt flow pattern in premature infants. Arch Dis Child Fetal Neonatal Ed 77:F36–F40CrossRefPubMed Su BH, Watanabe T, Shimizu M, Yanagisawa M (1997) Echocardiographic assessment of patent ductus arteriosus shunt flow pattern in premature infants. Arch Dis Child Fetal Neonatal Ed 77:F36–F40CrossRefPubMed
17.
Zurück zum Zitat Bancalari E, Claure N (2006) Definitions and diagnostic criteria for bronchopulmonary dysplasia. Semin Perinatol 30:164–170CrossRefPubMed Bancalari E, Claure N (2006) Definitions and diagnostic criteria for bronchopulmonary dysplasia. Semin Perinatol 30:164–170CrossRefPubMed
18.
Zurück zum Zitat Vento G, Matassa PG, Zecca E, Tortorolo L, Martelli M, De Carolis MP, Maggio L, Zini G, D’Onofrio G, Valentini S, Romagnoli C (2004) Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants. Pharmacology 71:113–119CrossRefPubMed Vento G, Matassa PG, Zecca E, Tortorolo L, Martelli M, De Carolis MP, Maggio L, Zini G, D’Onofrio G, Valentini S, Romagnoli C (2004) Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants. Pharmacology 71:113–119CrossRefPubMed
19.
Zurück zum Zitat Inzitari R, Vento G, Capoluongo E, Boccacci S, Fanali C, Cabras T, Romagnoli C, Giardina B, Messana I, Castagnola M (2007) Proteomic analysis of salivary acidic proline-rich proteins in human pre-term and at-term newborns. J Proteome Res 6:1371–1377CrossRefPubMed Inzitari R, Vento G, Capoluongo E, Boccacci S, Fanali C, Cabras T, Romagnoli C, Giardina B, Messana I, Castagnola M (2007) Proteomic analysis of salivary acidic proline-rich proteins in human pre-term and at-term newborns. J Proteome Res 6:1371–1377CrossRefPubMed
20.
Zurück zum Zitat Ong SE, Mann M (2005) Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol 1:252–262CrossRefPubMed Ong SE, Mann M (2005) Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol 1:252–262CrossRefPubMed
21.
Zurück zum Zitat Dargaville PA, South M, Vervaart P, McDougall PN (1999) Validity of markers of dilution in small volume lung lavage. Am J Respir Crit Care Med 160:778–784PubMed Dargaville PA, South M, Vervaart P, McDougall PN (1999) Validity of markers of dilution in small volume lung lavage. Am J Respir Crit Care Med 160:778–784PubMed
22.
Zurück zum Zitat Sellers A, Murphy G (1981) Collagenolytic enzymes and their naturally occurring inhibitors. Int Rev Connect Tissue Res 9:151–190PubMed Sellers A, Murphy G (1981) Collagenolytic enzymes and their naturally occurring inhibitors. Int Rev Connect Tissue Res 9:151–190PubMed
23.
Zurück zum Zitat Nerusu KC, Warner RL, Bhagavathula N, McClintock SD, Johnson KJ, Varani J (2007) Matrix metalloproteinase-3 (stromelysin-1) in acute inflammatory tissue injury. Exp Mol Pathol 83:169–176CrossRefPubMed Nerusu KC, Warner RL, Bhagavathula N, McClintock SD, Johnson KJ, Varani J (2007) Matrix metalloproteinase-3 (stromelysin-1) in acute inflammatory tissue injury. Exp Mol Pathol 83:169–176CrossRefPubMed
24.
Zurück zum Zitat Fligiel SE, Standiford T, Fligiel HM, Tashkin D, Strieter RM, Warner RL, Johnson KJ, Varani J (2006) Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury. Hum Pathol 37:422–430CrossRefPubMed Fligiel SE, Standiford T, Fligiel HM, Tashkin D, Strieter RM, Warner RL, Johnson KJ, Varani J (2006) Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury. Hum Pathol 37:422–430CrossRefPubMed
25.
Zurück zum Zitat Warner RL, Beltran L, Younkin EM, Lewis CS, Weiss SJ, Varani J, Johnson KJ (2001) Role of stromelysin 1 and gelatinase B in experimental acute lung injury. Am J Respir Cell Mol Biol 24:537–544PubMed Warner RL, Beltran L, Younkin EM, Lewis CS, Weiss SJ, Varani J, Johnson KJ (2001) Role of stromelysin 1 and gelatinase B in experimental acute lung injury. Am J Respir Cell Mol Biol 24:537–544PubMed
26.
Zurück zum Zitat Wang M, Qin X, Mudgett JS, Ferguson TA, Senior RM, Welgus HG (1999) Matrix metalloproteinase deficiencies affect contact hypersensitivity: stromelysin-1 deficiency prevents the response and gelatinase B deficiency prolongs the response. Proc Natl Acad Sci USA 96:6885–6889CrossRefPubMed Wang M, Qin X, Mudgett JS, Ferguson TA, Senior RM, Welgus HG (1999) Matrix metalloproteinase deficiencies affect contact hypersensitivity: stromelysin-1 deficiency prevents the response and gelatinase B deficiency prolongs the response. Proc Natl Acad Sci USA 96:6885–6889CrossRefPubMed
27.
Zurück zum Zitat Ekekezie II, Thibeault DW, Simon SD, Norberg M, Merrill JD, Ballard RA, Ballard PL, Truog WE (2004) Low levels of tissue inhibitors of matrix metalloproteinases with a high matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio are present in tracheal aspirate fluids of infants who develop CLD. Pediatrics 113:1709–1714CrossRefPubMed Ekekezie II, Thibeault DW, Simon SD, Norberg M, Merrill JD, Ballard RA, Ballard PL, Truog WE (2004) Low levels of tissue inhibitors of matrix metalloproteinases with a high matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio are present in tracheal aspirate fluids of infants who develop CLD. Pediatrics 113:1709–1714CrossRefPubMed
28.
Zurück zum Zitat Tambunting F, Beharry KD, Hartleroad J, Waltzman J, Stavitsky Y, Modanlou HD (2005) Increased lung matrix metalloproteinase-9 levels in extremely premature baboons with bronchopulmonary dysplasia. Pediatr Pulmonol 39:5–14CrossRefPubMed Tambunting F, Beharry KD, Hartleroad J, Waltzman J, Stavitsky Y, Modanlou HD (2005) Increased lung matrix metalloproteinase-9 levels in extremely premature baboons with bronchopulmonary dysplasia. Pediatr Pulmonol 39:5–14CrossRefPubMed
29.
Zurück zum Zitat Danan C, Jarreau PH, Franco ML, Dassieu G, Grillon C, Abd Alsamad I, Lafuma C, Harf A, Delacourt C (2002) Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 283:L1086–L1093PubMed Danan C, Jarreau PH, Franco ML, Dassieu G, Grillon C, Abd Alsamad I, Lafuma C, Harf A, Delacourt C (2002) Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 283:L1086–L1093PubMed
30.
Zurück zum Zitat Dik WA, van Kaam AH, Dekker T, Naber BA, Janssen DJ, Kroon AA, Zimmermann LJ, Versnel MA, Lutter R (2006) Early increased level of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome. Biol Neonate 89:6–14CrossRefPubMed Dik WA, van Kaam AH, Dekker T, Naber BA, Janssen DJ, Kroon AA, Zimmermann LJ, Versnel MA, Lutter R (2006) Early increased level of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome. Biol Neonate 89:6–14CrossRefPubMed
31.
Zurück zum Zitat Sweet DG, Curley AE, Chesshyre E, Pizzotti J, Wilbourn MS, Halliday HL, Warner JA (2004) The role of matrix metalloproteinases-9 and -2 in development of neonatal chronic lung disease. Acta Paediatr 93:791–796PubMedCrossRef Sweet DG, Curley AE, Chesshyre E, Pizzotti J, Wilbourn MS, Halliday HL, Warner JA (2004) The role of matrix metalloproteinases-9 and -2 in development of neonatal chronic lung disease. Acta Paediatr 93:791–796PubMedCrossRef
32.
Zurück zum Zitat Cederqvist K, Sorsa T, Tervahartiala T, Maisi P, Reunanen K, Lassus P, Andersson S (2001) Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics 108:686–692CrossRefPubMed Cederqvist K, Sorsa T, Tervahartiala T, Maisi P, Reunanen K, Lassus P, Andersson S (2001) Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics 108:686–692CrossRefPubMed
33.
Zurück zum Zitat Schulz CG, Sawicki G, Lemke RP, Roeten BM, Schulz R, Cheung PY (2004) MMP-2 and MMP-9 and their tissue inhibitors in the plasma of preterm and term neonates. Pediatr Res 55:794–801CrossRefPubMed Schulz CG, Sawicki G, Lemke RP, Roeten BM, Schulz R, Cheung PY (2004) MMP-2 and MMP-9 and their tissue inhibitors in the plasma of preterm and term neonates. Pediatr Res 55:794–801CrossRefPubMed
Metadaten
Titel
Bronchoalveolar lavage fluid peptidomics suggests a possible matrix metalloproteinase-3 role in bronchopulmonary dysplasia
verfasst von
Giovanni Vento
Chiara Tirone
Paola Lulli
Ettore Capoluongo
Franco Ameglio
Simona Lozzi
Francesco Cota
Fabio Mosca
Costantino Romagnoli
Irene Messana
Massimo Castagnola
Rosanna Inzitari
Publikationsdatum
01.12.2009
Verlag
Springer-Verlag
Erschienen in
Intensive Care Medicine / Ausgabe 12/2009
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-009-1646-6

Weitere Artikel der Ausgabe 12/2009

Intensive Care Medicine 12/2009 Zur Ausgabe

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.