Bronchoalveolar Lavage Fluid Proteome in Bronchiolitis Obliterans Syndrome: Possible Role for Surfactant Protein A in Disease Onset

Meloni, Federica; Salvini, Roberta; Bardoni, Anna Maria; Passadore, Ileana; Solari, Nadia; Vitulo, Patrizio; Oggionni, Tiberio; Viganò, Mario; Pozzi, Ernesto; Fietta, Anna Maria

doi:10.1016/j.healun.2007.08.009

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 26, Issue 11 , Pages 1135-1143, November 2007

Bronchoalveolar Lavage Fluid Proteome in Bronchiolitis Obliterans Syndrome: Possible Role for Surfactant Protein A in Disease Onset

Federica Meloni, MD
- Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia, Pavia, Italy
- Reprint requests: Federica Meloni, MD, Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, Policlinico San Matteo, Padiglione Forlanini, Via Taramelli 5, 27100 Pavia, Italy. Telephone: +39-0382-501008. Fax: +39-0382-422704.
Roberta Salvini, ScD
- Department of Biochemistry, University of Pavia, Pavia, Italy
Anna Maria Bardoni, ScD
- Department of Biochemistry, University of Pavia, Pavia, Italy
Ileana Passadore, ScD
- Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia, Pavia, Italy
Nadia Solari, ScD
- Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia, Pavia, Italy
Patrizio Vitulo, MD
- Pneumology Unit, ISMETT-UPMC, Palermo, Italy
Tiberio Oggionni, MD
- Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia, Pavia, Italy
Mario Viganò, MD
- Department of Cardiac Surgery, University of Pavia and IRCCS San Matteo Foundation, Pavia, Italy.
Ernesto Pozzi, MD
- Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia, Pavia, Italy
Anna Maria Fietta, ScD
- Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia, Pavia, Italy

Received 18 May 2007; received in revised form 18 July 2007; accepted 20 August 2007.

Background

Bronchiolitis obliterans syndrome (BOS) affects long-term survival of lung transplant (Tx) recipients (LTRs), with no consistently effective treatment strategy. Identifying early markers of BOS is of paramount importance for improving graft survival.

Methods

We used 2-dimensional gel electrophoresis and protein identification by mass spectrometry to compare the protein profile of bronchoalveolar lavage fluid (BALf) in two groups of LTRs: one composed of patients with BOS and the other composed of patients with good graft function at >5 years post-surgery (stable LTRs). Based on the hypothesis that only proteins of lung origin could represent reliable BOS markers, we also evaluated paired plasma samples. Proteins of interest were also assessed in the BALf of control subjects and results confirmed by dot- blot analysis.

Results

Among 11 differentially expressed proteins, we identified 2 locally produced factors: peroxiredoxin II (PRXII), exclusively expressed in BOS; and surfactant protein A (SP-A), expressed consistently less in BOS patients than in stable LTRs. PRXII expression was never observed in BALf from control subjects, whereas SP-A was present in higher amounts compared with stable LTRs and BOS patients. Finally, the time course of SP-A was studied in 5 LTRs who subsequently developed BOS. A reduction in BALf SP-A content was detectable early after Tx, preceding BOS onset in 4 of 5 patients.