Enzymes and receptors in the leukotriene cascade.

Leukotrienes are a family of paracrine hormones derived from the oxidative metabolism of arachidonic acid. These lipid mediators are recognized as important signal molecules in a variety of inflammatory and allergic conditions affecting the skin, joints, gastrointestinal and respiratory systems, in particular asthma. Such conditions are typified by local pain, tissue edema, hyperemia and functional losses. In the tissues, immunocompetent cells accumulate at the site of injury which contribute to tissue damage and perpetuation of the disease process. Leukotrienes can elicit most, if not all, of these signs and symptoms. Thus, leukotriene B4 is one of the most powerful chemotactic agents known to date and participates in the recruitment of leukocytes. The cysteinyl leukotrienes, on the other hand, contract smooth muscles, particularly in the peripheral airways and microcirculation. Recently, drugs which block the formation and action of leukotrienes have been introduced as novel antiasthmatic medications. This chapter reviews the biochemistry, molecular biology and cell biology of the key enzymes and cognate receptors in the leukotriene cascade.