Chapter 33 - Lipid Mediators from Mast Cells and Basophils in Allergic Diseases

Abstract

This chapter discusses the role of mast cells and basophils in allergic diseases. The pathophysiological functions of mast cells and basophils are largely mediated by the production of soluble molecules including pre-formed mediators, de novo synthesized lipid mediators, cytokines, and chemokines. Lipid mediators are pivotal molecules in initiating and maintaining the inflammatory response in allergic diseases. Mast cells and basophils produce two classes of lipid mediators: the metabolites of arachidonic acid collectively referred to as eicosanoids, and the group of 2-acetylated phospholipids, including platelet-activating factor (PAF) and related molecules. The two classes of lipid mediators are biochemically related, since both are derived from phospholipids containing arachidonic acid (AA) esterified at the sn-2 position (2-arachidonoyl phospholipids). Mast cells and basophils contain large quantities of this common precursor of eicosanoids and PAE Activation of the common biosynthetic pathway explains why the two classes of lipid mediators are often produced simultaneously by stimulated mast cells and basophils. The initial step in the biosynthetic pathway of lipid mediators is the hydrolysis of AA from 2-arachidonoyl phospholipids by an enzyme of the phospholipase A2 (PLA2) family. The overall picture has been made more complicated by the discovery of new enzymes of various pools of AA with different specificities and subcellular locations, and under the genetic control of lipid mediator synthesis and catabolism.