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-eicosatetraenoic acid (5-oxo-ETE) is a highly potent eosinophil chemoattractant in vitro. To determine whether this substance can induce pulmonary eosinophil infiltration in vivo, it was administered to Brown Norway rats by tracheal insufflation. Eosinophils were then counted in lung sections that had been immunostained with an antibody to eosinophil major basic protein. 5-Oxo-ETE induced a dramatic increase in the numbers of eosinophils (ED₅₀, 2.5 μg) around the walls of the airways, which reached maximal levels (five times control levels) between 15 and 24 h after administration, and then declined. LTB₄ also induced pulmonary eosinophil infiltration with a similar ED₅₀ but appeared to be somewhat less effective. In contrast, LTD₄ and LTE₄ were inactive. 5-Oxo-ETE-induced eosinophilia was unaffected by the LTB₄ and PAF antagonists LY255283 and WEB 2170, respectively. However, it was inhibited by 75% by monoclonal antibodies to CD49d (VLA-4) or CD11a (LFA-1) but was not significantly affected by an antibody to CD11b (Mac-1). In conclusion, 5-oxo-ETE induces pulmonary eosinophilia in Brown Norway rats, raising the possibility that it may be a physiological mediator of inflammation in asthma.