5-Oxo-6,8,11,14-eicosatetraenoic acid is a potent chemoattractant for human basophils.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Sturm
Gunter J
GJ
Department of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
Schuligoi
Rufina
R
Sturm
Eva M
EM
Royer
Julia F
JF
Lang-Loidolt
Doris
D
Stammberger
Heinz
H
Amann
Rainer
R
Peskar
Bernhard A
BA
Heinemann
Akos
A
D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001491:Basophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009994:Osmolar Concentration; D037342:Pertussis Toxin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018055:Receptors, Eicosanoid / Q000235:genetics
D001095:Arachidonic Acids; D002630:Chemotactic Factors; C504018:OXER1 protein, human; D012333:RNA, Messenger; D018055:Receptors, Eicosanoid; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D037342:Pertussis Toxin; D002118:Calcium