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.
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.
Nakajima
H
H
Department of Internal Medicine, Chiba University School of Medicine, Japan.
Sano
H
H
Nishimura
T
T
Yoshida
S
S
Iwamoto
I
I
D000280:Administration, Inhalation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D018799:Intercellular Adhesion Molecule-1; D007958:Leukocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D016029:Receptors, Very Late Antigen / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014132:Trachea / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D000941:Antigens; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1