Eotaxin-2 alters eosinophil integrin function via mitogen-activated protein kinases

Am J Respir Cell Mol Biol. 2002 Jun;26(6):645-9. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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


  • CCL24 protein, human
  • Chemokine CCL24
  • Chemokines, CC
  • Integrins
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases