Pulmonary tissue produces high amounts of prostaglandins (PG), leukotrienes (LT), and hydroxy fatty acids (HFA) in response to a number of stimuli or pathological states. These lipids have diverse biological activities. The goal of this study is two-fold: first to develop an understanding of factors that control the biosynthesis of these lipids and second to determine their role in the secretory and inflammatory processes of the lung. We have chosen to study the biosynthesis of these lipids in dog tracheal epithelial cells and to determine their role in control of Cl- and mucus secretion. Dog trachea cells make primarily PGD2 and a number of LTs. LTC4, LTB4 and two unknown LTs are also produced. While Cl- secretion appears to be primarily under control of PGD2 formation, other data suggest a regulatory role for the LTs. We intend to characterize further the LTs formed and relate them to Cl- secretion. We are also studying the possible role of these lipids in lymphocyte responses to mitogens and the involvement with protein kinase C.
