Secretory Phospholipases A2 Are Secreted From Ciliated Cells and Increase Mucin and Eicosanoid Secretion From Goblet Cells

BACKGROUND: Secretory phospholipases A(2) (sPLA(2)) 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 sPLA(2) generation and response. We wished to determine the primary source(s) of sPLA(2) 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 sPLA(2), 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 sPLA(2) to specific cells types was confirmed by confocal microscopy. RESULTS: sPLA(2) group IIa, V, and X messenger RNA expression was increased in ciliated-enriched cells (P<.001) but not in goblet-enriched cells. sPLA(2) were secreted from the apical (air) side of ciliated-enriched cells but not goblet-enriched cells (P<.001). Immunostaining of sPLA(2) V was strongly positive in ciliated-enriched cells but not in goblet-enriched cells. sPLA(2) released cysLTs from goblet-enriched cells but not from ciliated-enriched cells, and this result was greatest with sPLA(2) V (P<.05). sPLA(2) V increased goblet-enriched cell mucin secretion, which was inhibited by inhibitors of lipoxygenase or cyclooxygenase (P<.02). CONCLUSIONS: sPLA(2) 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.