BACKGROUND: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a chemoattractant for eosinophils and neutrophils, and the messenger RNA for its receptor, the oxo-eicosatetraenoic acid receptor (OXE), has been detected in several tissues. OBJECTIVES: This study aimed at clarifying the role of 5-oxo-ETE in the regulation of basophil function. METHODS: Basophil responses were determined in assays of flow-cytometric shape change, Ca(2+) flux, chemotaxis, and histamine release. Messenger RNA for OXE was detected by real-time PCR. RESULTS: We observed that human eosinophils were 3 to 10 times more sensitive to 5-oxo-ETE than neutrophils in flow-cytometric shape change and Ca(2+) flux assays, as estimated from the half-maximal responses of the cells. Basophils responded to 5-oxo-ETE in the shape change assay with a sensitivity similar to that of eosinophils. 5-Oxo-ETE was a weak inducer of Ca(2+) flux in basophils and did not cause histamine release but was a highly effective chemoattractant for basophils in the low nanomolar concentration range in a pertussis toxin-sensitive manner. In agreement with these functional studies, the messenger RNA for the 5-oxo-ETE receptor, OXE, was detectable in basophils as in monocytes, eosinophils, and neutrophils, but not in fibroblasts. Specimens from sinus mucosa, tonsils, and adenoids also contained detectable levels of messenger RNA for OXE. CONCLUSION: Our data suggest that 5-oxo-ETE is potentially involved in the regulation of basophil recruitment and might hence be a useful therapeutic target in atopic disease.
BACKGROUND: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a chemoattractant for eosinophils and neutrophils, and the messenger RNA for its receptor, the oxo-eicosatetraenoic acid receptor (OXE), has been detected in several tissues. OBJECTIVES: This study aimed at clarifying the role of 5-oxo-ETE in the regulation of basophil function. METHODS: Basophil responses were determined in assays of flow-cytometric shape change, Ca(2+) flux, chemotaxis, and histamine release. Messenger RNA for OXE was detected by real-time PCR. RESULTS: We observed that human eosinophils were 3 to 10 times more sensitive to 5-oxo-ETE than neutrophils in flow-cytometric shape change and Ca(2+) flux assays, as estimated from the half-maximal responses of the cells. Basophils responded to 5-oxo-ETE in the shape change assay with a sensitivity similar to that of eosinophils. 5-Oxo-ETE was a weak inducer of Ca(2+) flux in basophils and did not cause histamine release but was a highly effective chemoattractant for basophils in the low nanomolar concentration range in a pertussis toxin-sensitive manner. In agreement with these functional studies, the messenger RNA for the 5-oxo-ETE receptor, OXE, was detectable in basophils as in monocytes, eosinophils, and neutrophils, but not in fibroblasts. Specimens from sinus mucosa, tonsils, and adenoids also contained detectable levels of messenger RNA for OXE. CONCLUSION: Our data suggest that 5-oxo-ETE is potentially involved in the regulation of basophil recruitment and might hence be a useful therapeutic target in atopic disease.
Authors: Stephanie Hennen; Haibo Wang; Lucas Peters; Nicole Merten; Katharina Simon; Andreas Spinrath; Stefanie Blättermann; Rhalid Akkari; Ramona Schrage; Ralf Schröder; Daniel Schulz; Celine Vermeiren; Katrin Zimmermann; Stefan Kehraus; Christel Drewke; Alexander Pfeifer; Gabriele M König; Klaus Mohr; Michel Gillard; Christa E Müller; Q Richard Lu; Jesus Gomeza; Evi Kostenis Journal: Sci Signal Date: 2013-10-22 Impact factor: 8.192
Authors: Magnus Bäck; William S Powell; Sven-Erik Dahlén; Jeffrey M Drazen; Jilly F Evans; Charles N Serhan; Takao Shimizu; Takehiko Yokomizo; G Enrico Rovati Journal: Br J Pharmacol Date: 2014-07-12 Impact factor: 8.739