Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue

J Exp Med. 1994 Apr 1;179(4):1145-54. doi: 10.1084/jem.179.4.1145.

Abstract

To determine the role of vascular cell adhesion molecule 1 (VCAM-1)/very late activation antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1)/lymphocyte function-associated antigen 1 (LFA-1) interactions in causing antigen-induced eosinophil and T cell recruitment into the tissue, we studied the effect of the in vivo blocking of VCAM-1, ICAM-1, VLA-4, and LFA-1 by pretreatment with monoclonal antibodies (mAb) to these four adhesion molecules on the eosinophil and T cell infiltration of the trachea induced by antigen inhalation in mice. The in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, prevented antigen-induced eosinophil infiltration into the mouse trachea. On the contrary, the in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, increased blood eosinophil counts after antigen challenge, but did not affect blood eosinophil counts without antigen challenge in sensitized mice. Furthermore, the expression of VCAM-1 but not ICAM-1 was strongly induced on the endothelium of the trachea after antigen challenge. In addition, pretreatment with anti-IL-4 mAb decreased the antigen-induced VCAM-1 expression only by 27% and had no significant effect on antigen-induced eosinophil infiltration into the trachea. The in vivo blocking of VCAM-1 and VLA-4 inhibited antigen-induced CD4+ and CD8+ T cell infiltration into the trachea more potently than that of ICAM-1 and LFA-1. In contrast, regardless of antigen challenge, the in vivo blocking of LFA-1, but not of ICAM-1, increased blood lymphocyte counts more than that of VCAM-1 and VLA-4. These results indicate that VCAM-1/VLA-4 interaction plays a predominant role in controlling antigen-induced eosinophil and T cell recruitment into the tissue and that the induction of VCAM-1 expression on the endothelium at the site of allergic inflammation regulates this eosinophil and T cell recruitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens / administration & dosage
  • Antigens / immunology
  • Cell Adhesion Molecules / physiology*
  • Chemotaxis, Leukocyte
  • Eosinophils / physiology*
  • Female
  • Intercellular Adhesion Molecule-1
  • Leukocyte Count
  • Lymphocyte Function-Associated Antigen-1 / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Rats
  • Receptors, Very Late Antigen / physiology*
  • T-Lymphocytes / physiology*
  • Trachea / immunology
  • Vascular Cell Adhesion Molecule-1

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Cell Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Very Late Antigen
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1