The Role of Phospholipases A2 in Eicosanoid Generation and Airway Inflammation

The mammalian genome encodes several secreted phospholipases A 2 and cytosolic phospholipase A 2 . 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 A 2 are available or being prepared. Using all of these tools, we are exploring the possible role of each mammalian phospholipase A 2 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 A 2 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 A 2 in promoting airway inflammation.