A monoclonal antibody against very late activation antigen-4 inhibits eosinophil accumulation and late asthmatic response in a guinea pig model of asthma.
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.
Sagara
H
H
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Matsuda
H
H
Wada
N
N
Yagita
H
H
Fukuda
T
T
Okumura
K
K
Makino
S
S
Ra
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003429:Cross Reactions; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology; D004804:Eosinophils / Q000166:cytology; D005434:Flow Cytometry / Q000379:methods; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D015151:Immunoblotting; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology*; D008297:Male; D011233:Precipitin Tests; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1