Human eosinophil, but not neutrophil, adherence to IL-1-stimulated human umbilical vascular endothelial cells is alpha 4 beta 1 (very late antigen-4) dependent.
Eosinophils, through their ability to generate an array of potent mediators, are thought to be the major effector cells in a number of conditions, including parasitic infection, asthma, and other allergic diseases. The mechanism(s) by which eosinophils, as opposed to neutrophils, accumulate at inflammatory sites is unknown. One possible mechanism would be an eosinophil-specific pathway of adhesion to vascular endothelium. In this study we have demonstrated that human eosinophils, but not neutrophils, constitutively express alpha 4 beta 1 (CD49d/CD29). Expression was not increased on low density eosinophils or normal density cells stimulated with platelet-activating factor. Eosinophils, but not neutrophils, specifically adhered to COS cells transfected with vascular adhesion molecule-1 in a alpha 4 beta 1-dependent manner. Eosinophil, but not neutrophil, adhesion to IL-1 stimulated human umbilical vascular endothelial cells was significantly inhibited by alpha 4 beta 1 mAb at both 5 h (p less than 0.05) and 20 h (p less than 0.001). Inhibition of both resting and platelet-activating factor-(10(-7) M) stimulated eosinophil adhesion was observed. We conclude that the alpha 4 beta 1/vascular adhesion molecule-1 adhesion pathway may be involved in specific eosinophil, as opposed to neutrophil, migration into sites of eosinophilic inflammation.
Walsh
G M
GM
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, England.
Mermod
J J
JJ
Hartnell
A
A
Kay
A B
AB
Wardlaw
A J
AJ
D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1; D007375:Interleukin-1 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D012397:Rosette Formation; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D010972:Platelet Activating Factor; D019010:Vascular Cell Adhesion Molecule-1