title: Lysophosphatidic acid is detectable in human bronchoalveolar lavage fluids at baseline and increased after segmental allergen challenge.
abstract: BACKGROUND
  Lysophosphatidic acid (LPA) is a biologically active lysophospholipid and a component of normal plasma. LPA binds to receptors expressed on circulating and structural lung cells and affects cell growth and activation. Whether LPA is present in the lung has not been previously reported.
  
  
  OBJECTIVE
  To develop an assay to measure LPA in bronchoalveolar lavage (BAL) fluids, and to study the association between LPA and allergic airway inflammation.
  
  
  METHODS
  Seventeen allergic subjects underwent bronchoscopy and segmental allergen challenge, followed 18 h later by BAL. Supernatants were analysed for LPA content using liquid chromatography and mass spectroscopy. Expression of LPA receptors on primary bronchial epithelial cells was analysed by immunolabelling, and the effects of LPA on epithelial cell barrier function was investigated by measuring transepithelial resistance.
  
  
  RESULTS
  LPA was detectable in BAL from control lung segments, and significantly increased 18 h after allergen challenge. Polyunsaturated species of LPA were especially increased following segmental allergen challenge. LPA levels did not strongly correlate with the number or percentages of eosinophils, neutrophils of lymphocytes, whereas MIP-3alpha (CCL20) levels correlated significantly with the allergen-driven influx of lymphocytes. The levels of LPA from control sites correlated inversely with BAL protein content, suggesting that LPA promoted epithelial barrier integrity at baseline. Experiments using primary human bronchial epithelial cells confirmed that LPA tightened the epithelial cell barrier.
  
  
  CONCLUSIONS
  Lysophosphatidic acid is detectable in human BAL fluids at baseline and its expression increases during allergic inflammation. LPA does not appear to be a dominant chemoattractant for eosinophils or lymphocytes during allergic airway inflammation. In the absence of ongoing inflammation, LPA may promote epithelial barrier integrity.
authors.affiliation: Division of Pulmonary & Critical Care Medicine, The Johns Hopkins Asthma & Allergy Center, Baltimore, MD, USA. Steve_Georas@urmc.rochester.edu
authors.forename: S N
authors.initials: SN
authors.lastname: Georas
authors.forename: E
authors.initials: E
authors.lastname: Berdyshev
authors.forename: W
authors.initials: W
authors.lastname: Hubbard
authors.forename: I A
authors.initials: IA
authors.lastname: Gorshkova
authors.forename: P V
authors.initials: PV
authors.lastname: Usatyuk
authors.forename: B
authors.initials: B
authors.lastname: Saatian
authors.forename: A C
authors.initials: AC
authors.lastname: Myers
authors.forename: M A
authors.initials: MA
authors.lastname: Williams
authors.forename: H Q
authors.initials: HQ
authors.lastname: Xiao
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: V
authors.initials: V
authors.lastname: Natarajan
mesh_terms: D000328:Adult; D000485:Allergens; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D008246:Lysophospholipids / Q000032:analysis; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged
chemical_list: D000485:Allergens; D008246:Lysophospholipids; C032881:lysophosphatidic acid