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

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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.

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Acknowledgments

The authors thank the Intensive Care Unit nursing staff for their invaluable collaboration on this work. They also are thankful for the financial support of Università Cattolica in Rome, MIUR, the Italian National Research Council (CNR), Università di Cagliari, Regione Sardegna and thanks fo the Fondazione Banco di Sardegna, International Scientific Institute “Paolo VI” (ISI) for their programs of scientific research promotion and diffusion. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome, Italy

    Giovanni Vento, Chiara Tirone, Francesco Cota & Costantino Romagnoli

  2. Institute of Biochemistry and Clinical Biochemistry c/o Institute of Chemistry of Molecular Recognition (CNR) and International Scientific Institute (ISI), Paolo VI, Catholic University, Largo F. Vito 1, 00168, Rome, Italy

    Paola Lulli, Ettore Capoluongo, Franco Ameglio, Massimo Castagnola & Rosanna Inzitari

  3. Division of Neonatology, Ospedale Pediatrico Bambino Gesù, Piazza S. Onofrio, 4, 00165, Rome, Italy

    Simona Lozzi

  4. Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, University of Milan, Milan, Italy

    Fabio Mosca

  5. Department of Sciences Applied to Biosystems, Cagliari University, Monserrato Campus, 09042, Monserrato (CA), Italy

    Irene Messana

  6. Division of Neonatology, Department of Pediatrics, Policlinico A. Gemelli-Università Cattolica S. Cuore, Largo A. Gemelli 8, 00168, Rome, Italy

    Giovanni Vento

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  1. Giovanni Vento
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Correspondence to Giovanni Vento.

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Vento, G., Tirone, C., Lulli, P. et al. Bronchoalveolar lavage fluid peptidomics suggests a possible matrix metalloproteinase-3 role in bronchopulmonary dysplasia. Intensive Care Med 35, 2115–2124 (2009). https://doi.org/10.1007/s00134-009-1646-6

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  • DOI: https://doi.org/10.1007/s00134-009-1646-6

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