EFFECT OF MAST-CELL DEFICIENCY AND LEUKOTRIENE INHIBITION ON THE INFLUX OF EOSINOPHILS INDUCED BY EOTAXIN

Eosinophils are believed to be important cells in the pathogenesis of asthma and allergic disease, Mast cells and leukotrienes may play a ro le in eosinophil recruitment, Eotaxin was recently described as a spec ific chemoattractant for eosinophils, Therefore we examined the effect s of eotaxin on eosinophil flux in the mast cell-deficient WBB6F1/J-Ki t(W)/Kit(W-v) (W/W-v) mice and in mice treated with zileuton or ABT-76 1, specific 5-lipoxygenase inhibitors, Mice were injected intraperiton eally with eotaxin and at various times later the peritoneal cavities were lavaged and cell populations determined, Murine recombinant eotax in induced a dose-dependent increase in eosinophils, which reached a m aximum at 1-2 h and subsided at 4 h in both BALB/c and W/W-v littermat e control mice (no other cell population was altered), However, in eot axin-injected W/W-v mice, the peak of eosinophil influx: was delayed, peaking at 2 h, and a lower number of eosinophils was seen, The specif ic lipoxygenase inhibitors zileuton and ABT-761 given 30 min before eo taxin caused a 63-79% reduction in the level of eosinophils seen in th e lavage fluid, These data suggest that eotaxin may either be activati ng eosinophils to release leukotrienes or making them more responsive to leukotrienes. In addition, mast cells may be playing a role in the amplification of the eotaxin effect.