THE ROLE OF THE EOSINOPHIL-SELECTIVE CHEMOKINE, EOTAXIN, IN ALLERGIC AND NONALLERGIC AIRWAYS INFLAMMATION

Blood eosinophilia and tissue infiltration by eosinophils are frequent ly observed in allergic inflammation and parasitic infections. This se lective accumulation of eosinophils suggested the existence of endogen ous eosinophil-selective chemoattractants. We have recently discovered a novel eosinophil-selective chemoattractant which we called eotaxin in an animal model of allergic airways disease. Eotaxin is generated i n both allergic and non-allergic bronchopulmonary inflammation. The ea rly increase in eotaxin paralled eosinophil infiltration in the lung t issue in both models. An antibody to IL-5 suppressed lung eosinophilia , correlating with an inhibition of eosinophil release from bone marro w 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 obser ved in guinea-pig lung may be responsible for the basal lung eosinophi lia observed in this species. Allergen-inducted eotaxin was present ma inly in the epithelium and alveolar macrophages, as detected by immuno staining. In contrast there was no upregulation of eotaxin by the epit helial cells following the injection of Sephadex beads and the alveola r macrophage and mononuclear cells sui rounding the granuloma were the predominant positive staining cells. Eotaxin and related chemokines a cting through the CCR3 receptor may play a major role in eosinophil re cruitment in allergic inflammation and parasitic diseases and thus off er an attractive target for therapeutic intervention.