The role of the eosinophil-selective chemokine, eotaxin, in allergic and non-allergic airways inflammation.
Blood eosinophilia and tissue infiltration by eosinophils are frequently observed in allergic inflammation and parasitic infections. This selective accumulation of eosinophils suggested the existence of endogenous eosinophil-selective chemoattractants. We have discovered a novel eosinophil-selective chemoattractant which we called eotaxin in an animal model of allergic airways disease. Eotaxin is generated in both allergic and non-allergic bronchopulmonary inflammation. The early increase in eotaxin paralleled eosinophil infiltration in the lung tissue in both models. An antibody to IL-5 suppressed lung eosinophilia, correlating with an inhibition of eosinophil release from bone marrow, without affecting eotaxin generation. This suggests that endogenous IL-5 is important for eosinophil migration but does not appear to be a stimulus for eotaxin production. Constitutive levels of eotaxin observed in guinea-pig lung may be responsible for the basal lung eosinophilia observed in this species. Allergen-induced eotaxin was present mainly in the epithelium and alveolar macrophages, as detected by immunostaining. In contrast there was no upregulation of eotaxin by the epithelial cells following the injection of sephadex beads and the alveolar macrophage and mononuclear cells surrounding the granuloma were the predominant positive staining cells. Eotaxin and related chemokines acting through the CCR3 receptor may play a major role in eosinophil recruitment in allergic inflammation and parasitic diseases and thus offer and attractive target for therapeutic intervention.
Department of Applied Pharmacology, Imperial College School of Medicine, National Heart and Lung Institute, London, U.K.
D M
DM
Conroy
A A
AA
Humbles
S M
SM
Rankin
R T
RT
Palframan
P D
PD
Collins
D A
DA
Griffiths-Johnson
P J
PJ
Jose
T J
TJ
Williams
D000818:Animals; D001249:Asthma / Q000276:immunology*; D054413:Chemokine CCL11; D018925:Chemokines / Q000502:physiology*; D019742:Chemokines, CC; D016207:Cytokines / Q000502:physiology*; D004802:Eosinophilia; D004804:Eosinophils / Q000502:physiology*; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D019707:Receptors, Chemokine
D054413:Chemokine CCL11; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D019707:Receptors, Chemokine