title: Ligand density modulates eosinophil signaling and migration.
abstract: Eosinophils are a major component of the inflammatory response in persistent airway inflammation 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 modulates eosinophil function, we investigated the effect of fibronectin and vascular cell adhesion molecule 1 (VCAM-1) density on eosinophil migration and signaling via the p38 and extracellular regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) signaling pathways. There was a dose-dependent inhibition of eosinophil spreading and migration on increasing concentrations of fibronectin 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 fibronectin concentrations. Together, the results demonstrate that fibronectin but not VCAM-1 inhibits eosinophil migration and signaling.
authors.affiliation: Department of Pediatrics, University of Wisconsin, Madison 53706, USA.
authors.forename: A
authors.initials: A
authors.lastname: Holub
authors.forename: J
authors.initials: J
authors.lastname: Byrnes
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: L
authors.initials: L
authors.lastname: Dzaidzio
authors.forename: N
authors.initials: N
authors.lastname: Hogg
authors.forename: A
authors.initials: A
authors.lastname: Huttenlocher
mesh_terms: D000328:Adult; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000097:blood; D015848:Interleukin-5 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D005353:Fibronectins; D015848:Interleukin-5; D016209:Interleukin-8; D019010:Vascular Cell Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases