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Am. J. Respir. Cell Mol. Biol., Volume 23, Number 1, July, 2000 37-44

Cell-Specific Expression of Group X and Group V Secretory Phospholipases A2 in Human Lung Airway Epithelial Cells

Michael C. Seeds, Kendra A. Jones, R. Duncan Hite, Mark C. Willingham, Hermina M. Borgerink, Ralph D. Woodruff, David L. Bowton, and David A. Bass

Departments of Internal Medicine/Section on Pulmonary and Critical Care, Pathology, and Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Secretory phospholipase A2 (sPLA2) enzymes contribute to inflammatory injury in human lungs by several mechanisms, including eicosanoid production and hydrolytic damage to surfactant phospholipids. Several distinct sPLA2 genes have been described in human tissue but little is known regarding their presence, localization, or function(s) within lungs. We hypothesized that sPLA2s would have cell-specific distributions within lung. We used reverse transcriptase/polymerase chain reaction to identify sPLA2 messenger RNAs (mRNAs) in adult human lung tissue. Resulting complementary DNA (cDNA) sequences indicated that total lung extracts contained mRNA for Groups IB, IIA, V, and X sPLA2. An epithelial cell line, BEAS cells, expressed only Groups IIA, V, and X. We used these cDNAs to clone these enzymes, especially the recently described Group X and Group V enzymes. Digoxigenin-labeled complementary RNA probes were used to determine localization of each sPLA2 by in situ hybridization of human lung. Hybridization was strongly positive for Group X and Group V in airway epithelial cells, which failed to hybridize Group IB or IIA probes. Although four known mammalian sPLA2 isotypes were expressed in lung, only Group X and Group V sPLA2 mRNAs appear uniquely expressed in airway epithelium, suggesting they could provide a mechanism of pulmonary surfactant hydrolysis during lung injury.




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