The effect of anti-VLA-4 monoclonal antibody on eosinophil accumulation and leukotriene production in nasal mucosa.
Eosinophil derived leukotrienes and platelet activating factor are known to cause nasal swelling. Toxic proteins induce nasal hyperreactivity to non-specific stimuli including histamine. Recent studies strongly suggest that very late activation antigen-4 (VLA-4) on the eosinophil surface plays a prominent role in the recruitment of eosinophils from blood vessels and eosinophil locomotion in inflammatory tissues. To test this hypothesis, we examined the effect of a monoclonal antibody (mAb) to VLA-4 on eosinophil accumulation in nasal mucosa after antigen challenge in a guinea pig model. Here we have demonstrated that the mAb depressed the eosinophil accumulation in nasal mucosa. In addition, we have shown that this mAb also inhibited eosinophil activation and leukotriene production. Our results raise a possibility that eosinophils might be activated during the journey from bloodstream to inflammatory tissues by the adhesion to endothelial cells and fibronectin. VLA-4 might act as a signalling as well as an adhesion receptor on eosinophils.
Terada
N
N
Department of Otorhinolaryngology, Chiba University, School of Medicine, Japan.
Sagara
H
H
Yagita
H
H
Okumura
K
K
Makino
S
S
Konno
A
A
Yamashita
T
T
Togawa
K
K
Ra
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015815:Cell Adhesion Molecules; D004804:Eosinophils / Q000187:drug effects* / Q000648:ultrastructure; D006168:Guinea Pigs; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D009504:Neutrophils / Q000187:drug effects / Q000648:ultrastructure; D010972:Platelet Activating Factor / Q000187:drug effects; D006255:Rhinitis, Allergic, Seasonal / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D015289:Leukotrienes; D010972:Platelet Activating Factor