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

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 <or=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.