title: Proteome analysis of bronchoalveolar lavage in pulmonary langerhans cell histiocytosis.
abstract: BACKGROUND
  Pulmonary Langerhans-cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by clusters of Langerhans cells, organized in granulomas, in the walls of distal bronchioles. It is a diffuse lung disease related to tobacco smoking but otherwise of unknown etiopathogenesis.
  
  
  METHODS
  In this study we used a proteomic approach to analyze BAL protein composition of patients with PLCH and of healthy smoker and non-smoker controls to obtain insights into the pathogenetic mechanisms of the disease, to study the effect of cigarette smoking on susceptibility to PLCH and to identify potential new biomarkers.
  
  
  RESULTS
  Two-dimensional electrophoresis and image analysis revealed proteins that were differently expressed (quantitatively and qualitatively) in the three groups of subjects. The proteins were identified by mass spectrometry and have various functions (antioxidant, proinflammatory, antiprotease) and origins (plasma, locally produced, etc.). Many, such as protease inhibitors (human serpin B3) and antioxidant proteins (glutathione peroxidase and thioredoxin) are already linked to PLCH pathogenesis, whereas other proteins have never been associated with the disease. Interestingly, numerous proteolytic fragments of plasma proteins (including kininogen-1 N fragments and haptoglobin) were also identified and suggest increased proteolytic activity in this inflammatory lung disease. Differences in protein expression were found between the three groups and confirmed by Principal Component Analysis (PCA).
  
  
  CONCLUSIONS
  Analysis of BAL proteomes of PLCH patients and of smoker and non-smoker controls also proved to be useful for researching the pathogenetic mechanisms and for identifying biomarkers of this rare diffuse lung disease.
authors.affiliation: Respiratory Diseases Section, Department of Clinical Medicine and Immunological Sciences, University of Siena, Siena (Italy. bargagli2@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Landi
authors.forename: Elena
authors.initials: E
authors.lastname: Bargagli
authors.forename: Barbara
authors.initials: B
authors.lastname: Magi
authors.forename: Antje
authors.initials: A
authors.lastname: Prasse
authors.forename: Joachim
authors.initials: J
authors.lastname: Muller-Quernheim
authors.forename: Luca
authors.initials: L
authors.lastname: Bini
authors.forename: Paola
authors.initials: P
authors.lastname: Rottoli
references.citation: PLoS Med. 2007 Aug;4(8):e253
references.pmid: 17696642
references.citation: Pol Arch Med Wewn. 2010 Jul;120(7-8):270-5
references.pmid: 20693957
references.citation: J Physiol Pharmacol. 2008 Dec;59 Suppl 6:781-9
references.pmid: 19218705
references.citation: Anal Biochem. 1988 Sep;173(2):424-35
references.pmid: 3189820
references.citation: Electrophoresis. 1993 Dec;14(12):1357-65
references.pmid: 8137802
references.citation: Med Pediatr Oncol. 2002 Jan;38(1):70-1
references.pmid: 11835245
references.citation: Am J Surg. 2009 Jul;198(1):105-9
references.pmid: 19249732
references.citation: Sarcoidosis Vasc Diffuse Lung Dis. 2007 Mar;24(1):59-64
references.pmid: 18069420
references.citation: Anal Biochem. 1995 Jan 1;224(1):451-5
references.pmid: 7710111
references.citation: Respir Med. 2010 Jul;104 Suppl 1:S81-5
references.pmid: 20430602
references.citation: Am J Respir Crit Care Med. 2005 Dec 1;172(11):1383-92
references.pmid: 16166618
references.citation: Toxicol Lett. 2008 May 30;178(3):191-6
references.pmid: 18467043
references.citation: Trends Mol Med. 2009 Oct;15(10):461-7
references.pmid: 19783213
references.citation: J Cell Sci. 2004 Jun 1;117(Pt 13):2631-9
references.pmid: 15169834
references.citation: Eur Respir J. 2010 May;35(5):1130-6
references.pmid: 19741025
references.citation: Clin Sci (Lond). 2005 Mar;108(3):273-6
references.pmid: 15537394
references.citation: J Cell Mol Med. 2010 Jun;14(6A):1264-75
references.pmid: 19799649
references.citation: Am J Respir Cell Mol Biol. 2008 Jun;38(6):655-60
references.pmid: 18203971
references.citation: Int J Oncol. 2009 Jul;35(1):159-66
references.pmid: 19513563
references.citation: Respiration. 2007;74(5):481-92
references.pmid: 17671403
references.citation: J Cell Sci. 2006 May 1;119(Pt 9):1947-60
references.pmid: 16636079
references.citation: Immunol Lett. 2008 Nov 16;121(1):13-21
references.pmid: 18706444
references.citation: Respir Med. 2007 Oct;101(10):2176-81
references.pmid: 17631992
references.citation: Sci Transl Med. 2009 Oct 28;1(4):4ra10
references.pmid: 20368170
references.citation: Eur J Immunol. 2010 Mar;40(3):787-96
references.pmid: 20017193
references.citation: Proteomics. 2006 Dec;6(23):6354-69
references.pmid: 17133372
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Biochemistry. 1999 Feb 9;38(6):1757-64
references.pmid: 10026255
references.citation: Anal Biochem. 1988 Sep;173(2):412-23
references.pmid: 3189819
references.citation: J Toxicol Environ Health A. 2008;71(22):1490-8
references.pmid: 18836924
references.citation: J Pathol. 2009 Jan;217(1):54-64
references.pmid: 18798225
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Sep;299(3):L425-33
references.pmid: 20511341
references.citation: Am Rev Respir Dis. 1989 May;139(5):1112-7
references.pmid: 2712439
references.citation: Biochem Biophys Res Commun. 2005 Dec 2;337(4):1283-7
references.pmid: 16236264
references.citation: Am J Respir Crit Care Med. 2004 Aug 1;170(3):242-51
references.pmid: 15117744
references.citation: Chest. 2003 May;123(5):1673-83
references.pmid: 12740289
references.citation: Proteomics. 2005 Apr;5(5):1423-30
references.pmid: 15761959
references.citation: Eur Respir J. 2005 Aug;26(2):319-38
references.pmid: 16055882
references.citation: Anal Biochem. 1980 Jul 1;105(2):361-3
references.pmid: 6161559
references.citation: J Physiol Pharmacol. 2007 Nov;58 Suppl 5(Pt 2):767-80
references.pmid: 18204191
references.citation: J Proteomics. 2010 Jun 16;73(8):1511-22
references.pmid: 20230924
references.citation: Am J Respir Crit Care Med. 1999 Feb;159(2):473-9
references.pmid: 9927360
references.citation: J Chromatogr A. 2007 Jun 15;1153(1-2):235-58
references.pmid: 17276441
references.citation: Biochem Biophys Res Commun. 2009 Jan 23;378(4):821-5
references.pmid: 19070595
references.citation: Arthritis Rheum. 2004 Mar;50(3):976-84
references.pmid: 15022342
references.citation: Eur J Cancer. 2004 Jul;40(10):1467-73
references.pmid: 15196529
references.citation: N Engl J Med. 2000 Jun 29;342(26):1969-78
references.pmid: 10877650
references.citation: Respir Res. 2010 Apr 26;11:45
references.pmid: 20420706
references.citation: Immunol Rev. 2005 Aug;206:83-99
references.pmid: 16048543
references.citation: Ann Diagn Pathol. 2008 Dec;12(6):445-57
references.pmid: 18995211
references.citation: News Physiol Sci. 2003 Apr;18:60-4
references.pmid: 12644621
references.citation: Am J Respir Crit Care Med. 1996 Jan;153(1):426-35
references.pmid: 8542154
references.citation: Int J Chron Obstruct Pulmon Dis. 2010 Aug 09;5:217-22
references.pmid: 20714375
references.citation: J Immunol. 2009 Apr 15;182(8):4507-11
references.pmid: 19342622