Cloning of human airway 15-lipoxygenase: identity to the reticulocyte enzyme and expression in epithelium.

Lipoxygenases constitute a family of enzymes which are implicated in a variety of inflammatory disorders including asthma. Although the 15-lipoxygenase has been identified as the major route of arachidonic acid metabolism in human lung, airway epithelial cells, eosinophils, and developing red cells, the localization of the enzyme within lung has not been clearly defined. Furthermore, the existence of isoforms of 15-lipoxygenase in different tissues has recently been proposed. To address these issues, we isolated a 2.6-kb cDNA encoding human airway 15-lipoxygenase from a human bronchus cDNA library using a previously characterized reticulocyte 15-lipoxygenase cDNA as a probe. The airway 15-lipoxygenase sequence was found to be identical to that of the reticulocyte-derived clone. Immunocytochemical studies using an antibody to human recombinant 15-lipoxygenase specifically localizes the enzyme to the basal and ciliated cells of the trachea, bronchi, and bronchioles. Staining for 15-lipoxygenase is not present in the airway secretory epithelial cells, epithelial cells located in the gas-exchanging regions of lung, vascular structures, or inflammatory cells. Taken together these results suggest that the 15-lipoxygenase of human lung is identical to that of the reticulocyte enzyme and is preferentially expressed in airway epithelium.