title: Eotaxin-2 alters eosinophil integrin function via mitogen-activated protein kinases.
abstract: Adhesion molecules and chemokines contribute to selective eosinophil recruitment in allergic inflammation. In this study, we examined the effects of eotaxin-2, a CCR3-specific chemokine, on integrin-mediated eosinophil adhesion to vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), or both using a parallel plate flow system. Tissue culture plates were coated with various combinations of VCAM-1, ICAM-1, and/or eotaxin-2. Human eosinophils were infused at physiologic shear stress (0.5 dyn/cm(2)) for 10 min, and the numbers of attached eosinophils were monitored using video microscopy. Cells accumulated efficiently on VCAM-1 and even better on surfaces co-coated with VCAM-1 and ICAM-1, but poorly on surfaces coated with ICAM-1 or bovine serum albumin alone. When eotaxin-2 was co-immobilized with adhesion proteins, fewer cells adhered to VCAM-1 and more adhered to ICAM-1, whereas levels of attachment to VCAM-1 plus ICAM-1 showed no net change. However, experiments with adhesion molecule blocking monoclonal antibody showed that the contribution of ICAM-1-mediated adhesion was always greater if eotaxin-2 was present. Pretreatment of cells with a CCR3-blocking mAb, or PD98059, a MAP-kinase inhibitor, prevented the eotaxin-2-induced changes in eosinophil attachment. These data suggest that eotaxin-2, acting via MAP kinases, may facilitate eosinophil recruitment at sites of allergic inflammation by shifting their adhesion molecule usage away from VCAM-1-dominated to ICAM-1-dominated pathways.
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tachimoto
authors.forename: Matsuo
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Hudson
authors.forename: Carol A
authors.initials: CA
authors.lastname: Bickel
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hamilton
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Bochner
mesh_terms: D054423:Chemokine CCL24; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C515484:CCL24 protein, human; D054423:Chemokine CCL24; D019742:Chemokines, CC; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases