title: MRP14 is elevated in the bronchoalveolar lavage fluid of fibrosing interstitial lung diseases.
abstract: Pulmonary fibrosis is defined by an overgrowth of fibroblasts and extracellular matrix deposition, and results in respiratory dysfunction that is often fatal. It is the end stage in many chronic inflammatory interstitial lung diseases (ILD) such as sarcoidosis and idiopathic pulmonary fibrosis (IPF). The myeloid-related proteins (MRPs) belong to the S100 family of calcium-binding proteins and are highly expressed by neutrophils, macrophages and epithelial cells during chronic inflammation. MRP14 stimulates fibroblast proliferation in vitro and is expressed in granulomas from sarcoidosis patients. We hypothesized that MRP14 may be a biomarker for fibrotic interstitial lung diseases. The objective of this study was to investigate whether levels of MRP14 in the bronchoalveolar lavage fluid (BALF) of patients with sarcoidosis and IPF correlate with clinical parameters. We used an enzyme-linked immunosorbent assay (ELISA) to measure MRP14 in BALF of 74 sarcoidosis patients, 54 IPF patients and 19 controls. Mean BALF levels of MRP14 were elevated significantly in IPF (P < 0.001) and sarcoidosis (P < 0.05) patients compared to controls. MRP14 levels were associated linearly with sarcoidosis disease severity based on chest radiographic stage. Moreover, BALF MRP14 levels were correlated inversely with diffusion capacity and forced vital capacity in sarcoidosis patients. In IPF patients, a correlation with BALF neutrophil percentage was found. In conclusion, BALF MRP14 levels are elevated in IPF and sarcoidosis and are associated with disease severity in sarcoidosis. The results support the need for further studies into the role of MRP14 in the pathogenesis of lung fibrosis.
authors.affiliation: Center for Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital Nieuwegein, the Netherlands.
authors.forename: N M
authors.initials: NM
authors.lastname: Korthagen
authors.forename: M M
authors.initials: MM
authors.lastname: Nagtegaal
authors.forename: C H M
authors.initials: CH
authors.lastname: van Moorsel
authors.forename: K M
authors.initials: KM
authors.lastname: Kazemier
authors.forename: J M M
authors.initials: JM
authors.lastname: van den Bosch
authors.forename: J C
authors.initials: JC
authors.lastname: Grutters
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D040502:Calgranulin B / Q000032:analysis / Q000378:metabolism*; D002248:Carbon Monoxide / Q000378:metabolism; D002452:Cell Count; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D011653:Pulmonary Diffusing Capacity / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism*; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D014797:Vital Capacity / Q000502:physiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D040502:Calgranulin B; D002248:Carbon Monoxide