Eotaxin and RANTES enhance 5-oxo-6,8,11,14-eicosatetraenoic acid-induced eosinophil chemotaxis

Background: The 5-lipoxygenase product 5-oxo-6,8,11,14-eicosatetraenoic aci d (5-oxo-ETE) is a potent activator of human eosinophils and, among lipid m ediators, is the most active chemoattractant for these cells. Studies have demonstrated the importance of 5-lipoxygenase products in allergen-induced pulmonary eosinophilia. Because CC chemokines such as eotaxin and RANTES al so play critical roles in this phenomenon, it would seem likely that member s of both classes of mediators contribute to this response. Objective: The study was designed to directly compare the effects of 5-oxo- ETE on eosinophils with those of eotaxin and RANTES and to determine whethe r these chemokines could enhance the chemotactic response to 5-oxo-ETE, Methods: Eosinophil chemotaxis was measured with microchemotaxis chambers. CD11b, L-selectin, and actin polymerization were measured by flow cytometry , Calcium mobilization was measured by fluorescence. Results: 5-Oxo-ETE stimulated eosinophil chemotaxis with a potency between those of eotaxin and RANTES and a maximal response about 50% higher than th at of eotaxin, Threshold concentrations of eotaxin and RANTES increased the chemotactic potency of 5-oxo-ETE by more than 4-fold. 5-Oxo-ETE and eotaxi n were approximately equipotent in mobilizing cytosolic calcium in eosinoph ils, Eotaxin was more potent in inducing CD11b expression and actin polymer ization, but the maximal responses to 5-oxo-ETE were about 50% higher. 5-Ox o-ETE strongly induced L-selectin shedding, whereas eotaxin elicited only a weak and variable response, Conclusion: 5-Oxo-ETE is a strong activator of human eosinophils with a che motactic potency comparable to those of eotaxin and RANTES, both of which e nhance 5-oxo-ETE-induced chemotaxis. 5-Oxo-ETE and CC chemokines may combin e to induce pulmonary eosinophilia in asthma.