Eotaxin-2 Alters Eosinophil Integrin Function via Mitogen-Activated Protein Kinases

• Published in: American journal of respiratory cell and molecular biology Vol. 26; no. 6; pp. 645 - 649
• Main Authors: Tachimoto, Hiroshi, Kikuchi, Matsuo, Hudson, Sherry A, Bickel, Carol A, Hamilton, Robert G, Bochner, Bruce S
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01-06-2002; American Thoracic Society
• Subjects: Chemokine CCL24; Chemokines, CC - metabolism; Chemokines, CC - physiology; Eosinophils - physiology; Humans; Integrins - physiology; Intercellular Adhesion Molecule-1 - metabolism; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/ajrcmb.26.6.4741

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.