Source and Function of Keto Elaidic Acids from Lungs of Cotton Workers

Abstract

A series of cytotoxic oxygenated derivatives of oleic acid, 8-oxo-9, 9-oxo-10, 10-oxo-8-, and 11-oxo-9 trans octadecenoc acid, uniquely found at post-mortem in airway cells of cotton workers, were synthesized and shown to be cytotoxic, i.e., inhibitory of growth for several cell lines, including HL-60 and U-937 promyelocytes and Eagle's KB carcinoma cells. At μM concentrations, the B- and 11- keto acids: (1) are chemokinetic for human neutrophils; (2) activate production of O₂ and H₂O₂; (3) stimulate promyelocytes in culture to differentiate into neutrophils; and (4) increase diglyceride metabolism in inflammatory cells. These results indicate that these four monooxygenated fatty acids, which are found in airways of cotton workers and initiate both inflammation and differentiation in vitro, may be etiologic in the abnormal differentiation and inflammation seen in small airways of cotton workers.^4,5 This abnormal differentiation in bronchi may result from altered diglyceride metabolism with resultant activation of phosphoprotein kinase C initiated by the keto fatty acids.