Arachidonic acid metabolism in inflammatory cells of patients with bronchial asthma

Over the last few years, the demonstration of beneficial effects of leukotr iene receptor antagonists in various forms of asthma has renewed clinical a nd pharmacologic interest in this class of lipid mediators. Several studies demonstrated an increased biosynthesis of cysteinyl leukotrienes (CysLT) i n asthmatic patients. However, the reasons for the dysregulated production of CysLTs in asthmatic patients are not completely defined. An improved met hod of lipid mediator detection and the availability of cells isolated from human airways (by bronchoalveolar lavage [BAL] and bronchial biopsies) hav e allowed initial studies to address this issue. Eosinophils retrieved from inflamed airways of asthmatics have a larger arachidonic acid (AA) content than their blood counterpart. The high level of AA in these cells is prima rily due to a remodeling of endogenous arachidonate pools with the accumula tion of this fatty acid in a triglyceride-associated pool. In addition, ele vated levels of a secretory form of phospholipase AZ, the key enzyme initia ting the cascade of CysLTs, are found in the BAL of asthmatics. Finally, eo sinophils isolated from the BAL of asthmatics have an increased expression of LTC4 synthase. The level of expression of this enzyme correlates with th e increased amount of CysLTs produced in the airways of these patients. Tak en together, these data identify at least two possible mechanisms to explai n the excessive CysLT production in asthmatics: an increased content of AA in the glycerolipid pools of inflammatory cells an enhanced activity of key biosynthetic enzymes involved in CysLT synthesis.