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Department of Medicine, Section on Infectious Diseases, Wake Forest University Medical Center, Winston-Salem, NC 27157
5-Oxo-eicosatetraenoic acid (5-oxoETE) stimulated human neutrophil
(PMN) and eosinophil chemotaxis, PMN hexose uptake, and PMN membrane
GTP/GDP exchange. Pertussis toxin (PT), a blocker of heterotrimeric G
proteins (GP), completely inhibited these responses, but proved far
less effective on the same responses when elicited by leukotriene
B4, C5a, FMLP, platelet-activating factor, IL-8, or RANTES
chemotactic factors. 5-OxoETE also specifically bound to the membrane
preparations that conducted GTP/GDP exchange. This binding was
down-regulated by GTP
S, but not ADPS, and displaced by 5-oxoETE
analogues, but not by leukotriene B4, lipoxin
A4, or lipoxin B4. Finally, PMN expressed
PT-sensitive GP 
2 and PT-resistant GP
q/11- and 13-chains; eosinophils
expressed only i2 and q/11. We conclude
that 5-oxoETE activates granulocytes through a unique receptor that
couples preferentially to PT-sensitive GP. The strict dependency of
this putative receptor on PT-sensitive GP may underlie the limited
actions of 5-oxoETE, compared with other CF, and help clarify the
complex relations between receptors, GP, cell signals, and cell
responses.
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