title: Proteomic changes of alveolar lining fluid in illnesses associated with exposure to inhaled non-infectious microbial particles.
abstract: BACKGROUND
  Hyperresponsiveness to inhaled non-infectious microbial particles (NIMPs) has been associated with illnesses in the airways. Hypersensitivity pneumonitis (HP) is considered to be the prototype for these NIMPs-related diseases; however, there is no consensus on the definitions or diagnostic criteria for HP and the spectrum of related illnesses.
  
  
  RESULTS
  In order to identify the possible diagnostic markers for illnesses associated with NIMPs in alveolar lining fluid, we performed a proteomic analysis using a two-dimensional difference gel electrophoresis on bronchoalveolar lavage (BAL) fluid from patients with exposure to NIMPs in the context of damp building-related illness (DBRI) or conditions on the borderline to acute HP, designated here as agricultural type of microbial exposure (AME). Samples from patients with HP and sarcoidosis (SARC) were included for reference. Results were compared to results of healthy subjects (CTR). Western blot was used for validation of potential marker proteins from BAL fluid and plasma. Protein expression patterns suggest a close similarity between AME and HP, while DBRI was similar to CTR. However, in DBRI the levels of the inflammation associated molecules galectin-3 and alpha-1-antitrypsin were increased. A novel finding emerging from this study was the increases of semenogelin levels in BAL fluid from patients with AME, HP and SARC. Histone 4 levels were increased in AME, HP and SARC. Elevated plasma levels of histone 2B were detected in HP and SARC, suggesting it to be a potential blood indicator for inflammatory diseases of the lungs.
  
  
  CONCLUSIONS
  In this study, the proteomic changes in bronchoalveolar lavage of DBRI patients were distinct from other NIMP exposure associated lung diseases, while changes in AME overlapped those observed for HP patient samples. Some of the proteins identified in this study, semenogelin and histone 4, could function as diagnostic markers for differential diagnosis between DBRI and HP-like conditions.
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Teirilä
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Karvala
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Ahonen
authors.affiliation: Department of Pulmonology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Henrik
authors.initials: H
authors.lastname: Riska
authors.affiliation: Raasepori Health Care Center, Raasepori, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Pietinalho
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Tuominen
authors.affiliation: Unit of Clinical Physiology, Department of Clinical Physiology and Nuclear Medicine, Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Piirilä
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Puustinen
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001798:Blood Proteins; D016535:Bronchial Hyperreactivity / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D005260:Female; D037502:Galectin 3 / Q000378:metabolism; D037161:Galectins; D006657:Histones / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000009:adverse effects / Q000276:immunology*; D040901:Proteomics; D017565:Sarcoidosis, Pulmonary / Q000276:immunology / Q000473:pathology; D029607:Seminal Vesicle Secretory Proteins / Q000378:metabolism; D057825:Two-Dimensional Difference Gel Electrophoresis; D055815:Young Adult; D019896:alpha 1-Antitrypsin Deficiency / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; D006657:Histones; C428445:LGALS3 protein, human; D052638:Particulate Matter; D029607:Seminal Vesicle Secretory Proteins; C424482:seminal vesicle-specific antigen