title: Primary human airway epithelial cell-dependent inhibition of human lung mast cell degranulation.
abstract: BACKGROUND
  Chronic mast cell activation is a characteristic feature of asthma. BEAS-2B human airway epithelial cells (AEC) profoundly inhibit both constitutive and IgE-dependent human lung mast cell (HLMC) histamine release. The aim of this study was to examine the regulation of HLMC degranulation by primary AEC from healthy and asthmatic subjects, and investigate further the inhibitory mechanism.
  
  
  METHODS
  HLMC were co-cultured with both BEAS-2B and primary AEC grown as monolayers or air-liquid interface (ALI) cultures.
  
  
  RESULTS
  Both constitutive and IgE-dependent HLMC histamine release were attenuated by BEAS-2B, primary AEC monolayers and ALI cultures. This occurred in the absence of HLMC-AEC contact indicating the presence of a soluble factor. Unlike healthy ALI AEC, asthmatic ALI-AEC did not significantly reduce constitutive histamine release. AEC inhibitory activity was transferable in primary AEC monolayer supernatant, but less active than with Transwell co-culture, suggesting that the inhibitory factor was labile. The AEC inhibitory effects were attenuated by both AEC wounding and pertussis toxin, indicating the involvement of a G(0)/G(i) receptor coupled mechanism. Solid phase extraction of lipids (<10 kDa) removed the AEC inhibitory activity. The lipid derivatives resolving D1 and D2 and lipoxin A(4) attenuated HLMC histamine release in a dose-dependent fashion but were not detectable in co-culture supernatants.
  
  
  CONCLUSIONS
  Primary AEC suppress HLMC constitutive and IgE-dependent histamine secretion through the release of a soluble, labile lipid mediator(s) that signals through the G(0)/G(i) receptor coupled mechanism. Manipulation of this interaction may have a significant therapeutic role in asthma.
authors.affiliation: Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, United Kingdom. nmartin@doctors.org.uk
authors.forename: Neil
authors.initials: N
authors.lastname: Martin
authors.forename: Andrew
authors.initials: A
authors.lastname: Ruddick
authors.forename: Greer K
authors.initials: GK
authors.lastname: Arthur
authors.forename: Heidi
authors.initials: H
authors.lastname: Wan
authors.forename: Lucy
authors.initials: L
authors.lastname: Woodman
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.forename: Don J L
authors.initials: DJ
authors.lastname: Jones
authors.forename: Ian D
authors.initials: ID
authors.lastname: Pavord
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
mesh_terms: D001249:Asthma / Q000473:pathology; D015550:Cell Degranulation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism; D057230:Limit of Detection; D044045:Lipoxins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D008168:Lung / Q000473:pathology*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019899:Paracrine Communication; D037342:Pertussis Toxin / Q000494:pharmacology; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors / Q000378:metabolism; D020545:Respiratory Mucosa / Q000473:pathology*; D044004:Xanthones / Q000494:pharmacology
chemical_list: D018836:Inflammation Mediators; D044045:Lipoxins; D058307:Receptors, Prostaglandin E, EP2 Subtype; D044004:Xanthones; C040527:lipoxin A4; C518399:resolvin D1; C545423:resolvin D2; D004281:Docosahexaenoic Acids; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D007073:Immunoglobulin E; D037342:Pertussis Toxin