Lung eosinophilia is dependent on IL-5 and the adhesion molecules CD18 and VLA-4, in a guinea-pig model.
Blood and tissue-eosinophilia is a characteristic feature of a number of disease states. In experimental animals, the intravenous injection of parasitic larvae induces a profound eosinophilia that can be mimicked by the intravenous injection of Sephadex particles. In the present study, this procedure was used to investigate the mechanisms involved in the development of lung eosinophilia in a guinea-pig model. Intravenous administration of Sephadex particles to guinea-pigs resulted in a significant increase in the influx of eosinophils in the airways and in lung tissue eosinophil peroxidase (EPO) activity (at t = 24 hr). An anti-interleukin-5 (IL-5) monoclonal antibody (mAb) totally inhibited the eosinophilia in the airways and significantly reduced the lung tissue EPO activity. The concomitant accumulation of neutrophils and mononuclear cells, however, was not affected by this treatment. Monoclonal antibodies to VLA-4 and CD18 caused 58% and 62% suppression of eosinophilia in the bronchoalveolar lavage (BAL), respectively, whilst having no effect on lung tissue EPO activity. Co-administration of the two mAb resulted in total inhibition of eosinophil accumulation into BAL and significant suppression of lung tissue EPO activity (55% inhibition). This procedure also resulted in 72% inhibition of mononuclear cell influx and 68% inhibition of neutrophil influx in the BAL, the latter effect being entirely due to the actions of the anti-CD18 mAb. The results of this study indicate for the first time a requirement for IL-5 in the development of lung eosinophilia in this model. Further, it is clear that both the molecules VLA-4 and CD18 contribute to the development of this response and that maximal inhibition of lung eosinophilia is achieved only when the two adhesion pathways are simultaneously blocked.
Das
A M
AM
Department of Applied Pharmacology, National Heart & Lung Institute, London, UK.
Williams
T J
TJ
Lobb
R
R
Nourshargh
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003911:Dextrans; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000201:enzymology; D005260:Female; D006168:Guinea Pigs; D015848:Interleukin-5 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010544:Peroxidases / Q000378:metabolism; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D003911:Dextrans; D015848:Interleukin-5; D019010:Vascular Cell Adhesion Molecule-1; C025614:sephadex; D047209:Eosinophil Peroxidase; D010544:Peroxidases