title: Bronchoalveolar lavage neuregulin-1 is elevated in acute lung injury and correlates with inflammation.
abstract: Shedding of neuregulin (NRG)-1 from the pulmonary epithelium leads to activation of the epithelial human epidermal growth factor receptor (HER)2 receptor, increased pulmonary epithelial permeability and acute lung injury (ALI). We sought to determine whether NRG-1 was detectable and elevated in bronchoalveolar lavage (BAL) and plasma from patients with ALI compared with controls and to determine whether a correlation exists between NRG-1 and inflammation and outcome in ALI. Matched BAL and plasma samples were obtained from 23 ALI patients requiring intubation and mechanical ventilation. Control patients (n=5) included healthy volunteers. NRG-1 and indices of inflammation were measured in BAL and plasma via ELISA. The mean±sd BAL NRG-1 concentration in ALI patients was 187.0±21.35 pg·mL(-1) compared with 85.50±9.2 pg·mL(-1) in controls (p=0.001). Increased BAL NRG-1 was associated with markers of inflammation, and inversely correlated with ventilator-free days (VFDs; r= -0.51, p=0.015). Plasma NRG-1 was elevated in ALI patients compared with controls (611.7±354.2 versus 25.17±19.33 pg·mL(-1), p<0.001) and inversely correlated with VFDs (r= -0.51, p=0.04). These results confirm shedding of NRG-1 in ALI and suggest that the NRG-1-HER2 pathway is active in patients with ALI.
authors.affiliation: Dept. of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. FiniganJ@NJHealth.org
authors.forename: James H
authors.initials: JH
authors.lastname: Finigan
authors.forename: Rangnath
authors.initials: R
authors.lastname: Mishra
authors.forename: Vihas T
authors.initials: VT
authors.lastname: Vasu
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Silveira
authors.forename: David E
authors.initials: DE
authors.lastname: Nethery
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Standiford
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Burnham
authors.forename: Marc
authors.initials: M
authors.lastname: Moss
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kern
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D016022:Case-Control Studies; D004848:Epithelium / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012121:Respiration, Artificial
chemical_list: D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human