CHANGES IN CD11B AND L-SELECTIN EXPRESSION ON EOSINOPHILS ARE MEDIATED BY HUMAN LUNG FIBROBLASTS IN-VITRO

Eosinophilic airway infiltration is a central feature in asthma. Eosin ophils recovered from bronchoalveolar fluid show an activated phenotyp e, e.g., increased CD11b and decreased L-selectin expression. We inves tigated whether lung fibroblasts are able to activate eosinophils in v itro, and if so, which activating factor is most important. CD11b and L-selectin expression of isolated peripheral blood eosinophils were me asured by flow cytometry after coculture with normal lung fibroblasts or their conditioned medium. We found that eosinophil CD11b expression increased (154% and 210%, p < 0.05) and L-selectin expression decreas ed (59% and 35.5%, p < 0.05) on eosinophils compared with baseline (10 0%) after 4 and 24 h of coculture with interleukin-1-beta (IL-1 beta)- stimulated fibroblasts, respectively. Conditioned medium of stimulated fibroblasts also increased CD11b expression, but to a smaller extent (p < 0.05). L-selectin expression of eosinophils in cocultures was not different from that of eosinophils in conditioned medium. Only anti-g ranulocyte/macrophage colony-stimulating factor (anti-GM-CSF) reduced the activation of eosinophils in conditioned medium to almost basal le vels (p < 0.05). An increase in CD11b expression is mediated by cytoki nes as well as direct cell contact, whereas a decrease in L-selectin e xpression is only mediated by cytokines. GM-CSF released by fibroblast s is an important factor in the modulation of both CD11b and L-selecti n expression. These results show that lung fibroblasts can activate eo sinophils by both adhesive interactions and by soluble factors.