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 role in eosinophil recruitment. Eotaxin was recently described as a specific chemoattractant for eosinophils. Therefore we examined the effects of eotaxin on eosinophil flux in the mast cell-deficient WBB6F1/J-KitW/ KitW-v (W/Wv) mice and in mice treated with zileuton or ABT-761, specific 5-lipoxygenase inhibitors. Mice were injected intraperitoneally with eotaxin and at various times later the peritoneal cavities were lavaged and cell populations determined. Murine recombinant eotaxin induced a dose-dependent increase in eosinophils, which reached a maximum at 1-2 h and subsided at 4 h in both BALB/c and W/WV littermate control mice (no other cell population was altered). However, in eotaxin-injected W/Wv mice, the peak of eosinophil influx was delayed, peaking at 2 h, and a lower number of eosinophils was seen. The specific lipoxygenase inhibitors zileuton and ABT-761 given 30 min before eotaxin caused a 63-79% reduction in the level of eosinophils seen in the lavage fluid. These data suggest that eotaxin may either be activating 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.
Harris
R R
RR
Immunoscience Research, Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.
Komater
V A
VA
Marett
R A
RA
Wilcox
D M
DM
Bell
R L
RL
D000818:Animals; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology*; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000096:biosynthesis / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; C096921:atreleuton; C063449:zileuton; D006918:Hydroxyurea