Ligand density modulates eosinophil signaling and migration

Abstract: Eosinophils are a major component of the inflammatory response in persistent airway in-flammation in asthma. The factors that determine the retention of eosinophils in the airway remain poorly understood. Elevated levels of fibronectin have been observed in the airway of patients with asthma, and the levels correlate with eosinophil numbers. To determine if fibronectin density mod-ulates eosinophil function, we investigated the ef-fect of fibronectin and vascular cell adhesion mol-ecule 1 (VCAM-1) density on eosinophil migration and signaling via the p38 and extracellular regu-lated kinase (ERK)–mitogen-activated protein ki-nase (MAPK) signaling pathways. There was a dose-dependent inhibition of eosinophil spreading and migration on increasing concentrations of fi-bronectin but not VCAM-1. In addition, activation of p38 MAPK was inhibited at high fibronectin but not high VCAM-1 concentrations, and ERK activity was slightly reduced at high VCAM-1 and fibronec-tin concentrations. Together, the results demon-strate that fibronectin but not VCAM-1 inhibits eo-sinophil migration and signaling. J. Leukoc. Biol