title: Secretory phospholipases A2 are secreted from ciliated cells and increase mucin and eicosanoid secretion from goblet cells.
abstract: BACKGROUND
  Secretory phospholipases A2 (sPLA2) initiate the biosynthesis of eicosanoids, are increased in the airways of people with severe asthma, and induce mucin hypersecretion. We used IL-13-transformed, highly enriched goblet cells and differentiated (ciliary cell-enriched) human bronchial epithelial cell culture to evaluate the relative contribution of ciliated and goblet cells to airway sPLA2 generation and response. We wished to determine the primary source(s) of sPLA2 and leukotrienes in human airway epithelial cells.
  
  
  METHODS
  Human bronchial epithelial cells from subjects without lung disease were differentiated to a ciliated-enriched or goblet-enriched cell phenotype. Synthesis of sPLA2, cysteinyl leukotrienes (cysLTs), and airway mucin messenger RNA and protein was measured by real-time-polymerase chain reaction and an enzyme-linked immunosorbent assay, and the localization of mucin and sPLA2 to specific cells types was confirmed by confocal microscopy.
  
  
  RESULTS
  sPLA2 group IIa, V, and X messenger RNA expression was increased in ciliated-enriched cells (P < .001) but not in goblet-enriched cells. sPLA2 were secreted from the apical (air) side of ciliated-enriched cells but not goblet-enriched cells (P < .001). Immunostaining of sPLA2 V was strongly positive in ciliated-enriched cells but not in goblet-enriched cells. sPLA2 released cysLTs from goblet-enriched cells but not from ciliated-enriched cells, and this result was greatest with sPLA2 V (P < .05). sPLA2 V increased goblet-enriched cell mucin secretion, which was inhibited by inhibitors of lipoxygenase or cyclooxygenase (P < .02).
  
  
  CONCLUSIONS
  sPLA2 are secreted from ciliated cells and appear to induce mucin and cysLT secretion from goblet cells, strongly suggesting that airway goblet cells are proinflammatory effector cells.
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA. Electronic address: ttanabe16@gmail.com.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Shimokawaji
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kanoh
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Rubin
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D009077:Mucins / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology; D054467:Phospholipases A2 / Q000378:metabolism*
chemical_list: D015777:Eicosanoids; D018793:Interleukin-13; D016209:Interleukin-8; D015289:Leukotrienes; D009077:Mucins; D054467:Phospholipases A2; D015232:Dinoprostone