A monoclonal antibody against very late activation antigen-4 inhibits eosinophil accumulation and late asthmatic response in a guinea pig model of asthma

Int Arch Allergy Immunol. 1997 Mar;112(3):287-94. doi: 10.1159/000237468.


Preferential eosinophil accumulation is a characteristic of airway inflammation in asthma. Although little is known about its mechanism, recent in vitro observations suggest that the very late activation antigen-4 (VLA-4, CD49d/CD29) and vascular cell adhesion molecule-1 (VCAM-1) adhesion pathway may be involved in specific eosinophil migration. To test this hypothesis, we studied the effect of an anti-VLA-4 monoclonal antibody (mAb) on the airway eosinophilia in a guinea pig model of asthma. Guinea pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed a striking airway eosinophilia and late asthmatic response (LAR). In contrast, when guinea pigs were pretreated intravenously at 2 h before antigen challenge with a rat antimouse VLA-4 mAb, PS2/3, cross-reacting with guinea pig eosinophils and lymphocytes, eosinophil, basophil and lymphocyte infiltration in the tracheal wall was significantly inhibited as well as LAR in a dose-dependent manner. These results suggest that VLA-4 plays a critical role in antigen-induced airway eosinophilia and LAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Asthma / immunology*
  • Asthma / prevention & control
  • Cell Adhesion / immunology
  • Cell Movement / immunology
  • Cross Reactions
  • Disease Models, Animal
  • Endothelium, Vascular / cytology
  • Eosinophils / cytology
  • Flow Cytometry / methods
  • Fluorescent Antibody Technique
  • Guinea Pigs
  • Immunoblotting
  • Integrin alpha4beta1
  • Integrins / immunology*
  • Male
  • Precipitin Tests
  • Receptors, Lymphocyte Homing / immunology*
  • Vascular Cell Adhesion Molecule-1 / physiology


  • Antibodies, Monoclonal
  • Integrin alpha4beta1
  • Integrins
  • Receptors, Lymphocyte Homing
  • Vascular Cell Adhesion Molecule-1