The cellular biology of eosinophil eicosanoid formation and function

Abstract

Eosinophils are capable of generating eicosanoid derivatives of arachidonic acid by means of cyclooxygenase and the 5- and 15-lipoxygenase (LO) pathways. Moreover, eosinophils, because of their expression of leukotriene (LT) C(4) synthase, are a major source of 5-LO-derived cysteinyl LTs, which are potent paracrine mediators of bronchial obstruction and inflammation pertinent to asthma. The regulation of eicosanoid formation within eosinophils involves activation of key enzymes at specific intracellular sites. Calcium ionophore-elicited translocation of 5-LO to the membranes of the nuclear envelope is associated with LTC(4) formation. In addition, lipid bodies, the formation of which is initiated by specific receptor-mediated signaling pathways, are sites of cyclooxygenase- and LO-pathway eicosanoid formation. Newly formed LTC(4) can be immunolocalized at perinuclear membranes in ionophore-activated eosinophils and at lipid bodies in CCR3 agonist (eg, eotaxin) chemokine-stimulated eosinophils. The local generation of eicosanoids at distinct sites within eosinophils may be important for the roles of these eicosanoids, both as paracrine mediators pertinent to inflammation and as intracrine signal-transducing mediators that help regulate cellular responses of eosinophils.