Eosinophil trafficking in asthma

Asthma is characterised by a 50-fold increase in the number of eosinophils relative to neutrophils in the bronchial mucosa. This is the result of the cumulative and sequential effects of several, approximately fourfold, incre ases in selective eosinophil versus neutrophil migration occurring at a num ber of stages in the life cycle of the eosinophil. These events, which are integrated and directed by allergen-specific T helper 2 lymphocytes through the generation of interleukin (IL)-5, IL-4 and IL-13, include: . effects on the bone marrow, mediated principally by IL-5, which result in a fourfold increase in circulating eosinophils . selective tethering of eosinophils to venular endothelium through the com bined effects of P-selectin/P-selectin glycoprotein ligand (PSGL)-1 and ver y late activation antigen (VLA)-4/vascular cell adhesion molecule-1, which has the potential for an up to tenfold increase in eosinophil versus neutro phil adhesion . selective chemotaxis under the influence of CC chemokines . prolonged survival, again mediated by IL-5. . The implications of this multistep process are that antagonists of IL-5, VLA-4, PSGL-1 and CC chemokine receptor 3, as well as IL-4 and IL-13, each have the potential markedly to inhibit eosinophil recruitment in asthma.