Title: The Role of Phospholipases A2 in Eicosanoid Generation and Airway Inflammation
Abstract:The mammalian genome encodes several secreted phospholipases A2 and cytosolic phospholipase A2. All of these enzymes have been obtained in recombinant form and their in vitro interfacial enzymatic pro...The mammalian genome encodes several secreted phospholipases A2 and cytosolic phospholipase A2. All of these enzymes have been obtained in recombinant form and their in vitro interfacial enzymatic properties studied. Inhibitors of these enzymes are being developed by structure-based approaches. Mice deficient in each of the phospholipases A2 are available or being prepared. Using all of these tools, we are exploring the possible role of each mammalian phospholipase A2 in liberating arachidonic acid from cellular membranes as the first step in the biosynthetic pathway leading to eicosanoids (prostaglandins and leukotrienes). Studies will be presented showing that the mode of phospholipase A2 action is determined by its membrane binding properties. We are also studying a mouse model of allergic asthma to reveal the role of specific phospholipases A2 in promoting airway inflammation.Read More