5-oxo-ETE induces pulmonary eosinophilia in an integrin-dependent manner in brown Norway rats

We have shown previously that the 5-lipoxygenase product 5-oxo-6,8,11,14-ei cosatetraenoic acid (5-oxo-ETE) is a highly potent eosinophil chemoattracta nt in vitro. To determine whether this substance can induce pulmonary eosin ophil infiltration in vivo, it was administered to Brown Norway rats by tra cheal insufflation. Eosinophils were then counted in lung sections that had been immunostained with an antibody to eosinophil major basic protein. 5-O xo-ETE induced a dramatic increase in the numbers of eosinophils (ED50, 2.5 mu g) around the walls of the airways, which reached maximal levels (five times control levels) between 15 and 24 h after administration, and then de clined. LTB4 also induced pulmonary eosinophil infiltration with a similar ED50 but appeared to be somewhat less effective, In contrast, LTD4 and LTE, were inactive, 5-Oxo-ETE-induced eosinophilia was unaffected by the LTB4 a nd PAF antagonists LY255283 and WEB 2170, respectively. However, it was inh ibited by similar to 75% by monoclonal antibodies to CD49d (VLA-4) or CD11a (LFA-1) but was not significantly affected by an antibody to CD11b (Mac-l) . In conclusion, 5-oxo-ETE induces pulmonary eosinophilia in Brown Norway r ats, raising the possibility that it may be a physiological mediator of inf lammation in asthma.