EFFECT OF INTERLEUKIN-5 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATINGFACTOR ON IN-VITRO EOSINOPHIL FUNCTION - COMPARISON WITH AIRWAY EOSINOPHILS

Eosinophils are hypothesized to be crucial in the development of aller gic airway inflammation; however, the actual mechanisms that determine their inflammatory activity are still largely undefined. To investiga te the factors that regulate eosinophil function in allergic airway di sease, we have previously used segmental bronchoprovocation with aller gen to study ex vivo eosinophil function. To determine whether the fun ctional changes associated with airway eosinophils obtained by broncho alveolar lavage 48 hours after antigen challenge are caused by exposur e to airway-generated cytokines, normodense blood eosinophils were cul tured in vitro with recombinant human interleukin-5 (IL-5) or granuloc yte-macrophage colony stimulating factor (GM-CSF). The effect of cytok ine exposure was then evaluated on selected cell functions. In vitro i ncubation with these cytokines for 24 hours significantly increased eo sinophil membrane expression of CD18 and CD11b compared with culture i n medium alone ol eosinophils obtained by bronchoalveolar lavage. N-fo rmyl-methionyl-leucyl-phenylalanine-stimulated superoxide anion genera tion was slightly but significantly enhanced by incubation with IL-5 b ur not with GM-CSF. In addition, spontaneous adhesion to human umbilic al vein endothelial cell monolayers was increased after exposure to bo th IL-5 and GM-CSF. However, activated adhesion was enhanced only by c ulture with IL-5 and stimulation with N-formyl-methionyl-leucyl-phenyl alanine. The magnitude of functional changes after in vitro preincubat ion of eosinophils with these cytokines did not achieve levels of supe roxide anion and adhesion noted with airway eosinophils obtained after segmental bronchoprovocation with allergen. These observations raise the possibility that the contribution of IL-5 and GM-CSF to phenotypic changes of airway eosinophils is principally to enhance survival and expression of adhesion proteins. These data also suggest that, in addi tion to the generation of proinflammatory cytokines, other factors con tribute to phenotypic changes in eosinophils as they migrate from the blood to the airway.