Eosinophils, trafficking and allergic inflammation (LL1-6)

The interaction of eosinophils and vascular endothelial cells are important early events in the sequestration of eosinophils to sites of allergic inflammation. Several cytokines including those elaborated by Th2 cells play a critical role in the regulation of adhesion molecule-mediated eosinophil rolling, adhesion and transmigration in vivo. Intravital microscopy studies of eosinophil trafficking in allergen challenged mice have revealed that chemokines/chemoattractants such as eotaxin, serotonin, C3a and their receptors differentially induce eosinophil adhesion and their recruitment to sites of allergic inflammation. In addition to the known contribution of selectins, integrins and molecules such as VCAM-1 and ICAM-1 to eosinophil trafficking and the onset of allergic inflammation, our recent studies have determined that Galectin-3 can function as a cell surface adhesion molecule by interacting with N-glycans elaborated by the enzyme Mgat5 to mediate eosinophil recruitment and Th2 driven airway allergic disease including airway remodeling. We have also demonstrated that endothelial expressed NDST-1, a key enzyme in the biosynthetic pathway of heparan sulfate chains, plays a critical role in the trafficking and recruitment of inflammatory leukocytes during episodes of airway allergic inflammation. In this presentation, the relative contribution of various cell adhesion molecules and the novel role played by Gal-3, Mgat-5 and NDST-1 in promoting eosinophil trafficking and recruitment and their role in allergic inflammation will be discussed.