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High-Throughput 2019, 8(1), 5; https://doi.org/10.3390/ht8010005

A Pilot Study to Investigate the Balance between Proteases and α1-Antitrypsin in Bronchoalveolar Lavage Fluid of Lung Transplant Recipients

1
Department of Molecular Medicine, Biochemistry Unit, University of Pavia, 27100 Pavia, Italy
2
Department of Internal Medicine and Therapeutics, Section of Pneumology, University of Pavia, 27100 Pavia, Italy
3
IRCCS Foundation Policlinico San Matteo, Department of Medical Sciences and Infective Diseases, Unit of Respiratory Diseases, 27100 Pavia, Italy
4
Department of Biology and Biotechnologies “L. Spallanzani″, Biochemistry Unit, University of Pavia, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 11 December 2018 / Revised: 30 January 2019 / Accepted: 7 February 2019 / Published: 13 February 2019
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Abstract

The neutrophilic component in bronchiolitis obliterans syndrome (BOS, the main form of chronic lung rejection), plays a crucial role in the pathogenesis and maintenance of the disorder. Human Neutrophil Elastase (HNE), a serine protease responsible of elastin degradation whose action is counteracted by α1-antitrypsin (AAT), a serum inhibitor specific for this protease. This work aimed to investigate the relationship between HNE and AAT in bronchoalveolar lavage fluid (BALf) from stable lung transplant recipients and BOS patients to understand whether the imbalance between proteases and inhibitors is relevant to the development of BOS. To reach this goal a multidisciplinary procedure was applied which included: (i) the use of electrophoresis/western blotting coupled with liquid chromatography-mass spectrometric analysis; (ii) the functional evaluation of the residual antiprotease activity, and (iii) a neutrophil count. The results of these experiments demonstrated, for the first time, the presence of the complex between HNE and AAT in a number of BALf samples. The lack of this complex in a few specimens analyzed was investigated in relation to a patient’s lung inflammation. The neutrophil count and the determination of HNE and AAT activities allowed us to speculate that the presence of the complex correlated with the level of lung inflammation. View Full-Text
Keywords: alpha 1-antitrypsin; bronchoalveolar lavage fluid; bronchiolitis obliterans syndrome; neutrophils; elastase; lung alpha 1-antitrypsin; bronchoalveolar lavage fluid; bronchiolitis obliterans syndrome; neutrophils; elastase; lung
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Cagnone, M.; Piloni, D.; Ferrarotti, I.; Di Venere, M.; Viglio, S.; Magni, S.; Bardoni, A.; Salvini, R.; Fumagalli, M.; Iadarola, P.; Martinello, S.; Meloni, F. A Pilot Study to Investigate the Balance between Proteases and α1-Antitrypsin in Bronchoalveolar Lavage Fluid of Lung Transplant Recipients. High-Throughput 2019, 8, 5.

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