Effect of 12-hydroxyeicosatetraenoic acid on cytosolic calcium in human neutrophils.
12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) has been reported to be a chemoattractant for human neutrophils. To assess its cellular mechanism, we focused on the effect of 12-HETE on cytosolic Ca2+ ([Ca2+]i) and characterized the effect of 12-HETE on [Ca2+]i in human neutrophils. 12(S)- and 12(R)-HETE increased [Ca2+]i in the presence and absence of extracellular Ca2+ in a concentration-related fashion. The elevation of [Ca2+]i by 12(R)-HETE was completely abolished by pertussis toxin treatment. U-73122, a selective phospholipase C inhibitor, depressed the 12(S)- and 12(R)-HETE-induced rise in [Ca2+]i in the presence and absence of extracellular Ca2+. 12(R)-HETE resulted in the rapid production of inositol 1,4,5-trisphosphate (IP3). Furthermore, 12(R)-HETE elicited slight depolarization of neutrophils as assessed using the fluorescent dye bis-oxonol. These results provide evidence demonstrating the signal transduction pathway in human neutrophils after stimulation with 12-HETE and suggest that 12-HETE causes a rapid rise of [Ca2+]i by mobilizing Ca2+ from an IP3-sensitive intracellular Ca2+ pool in human neutrophils.
Yoshino
H
H
Department of Periodontics, Hiroshima University School of Dentistry, Japan.
Kitayama
S
S
Morita
K
K
Uchiyama
Y
Y
Shibata
K
K
Shirakawa
M
M
Okamoto
H
H
Tsujimoto
A
A
Dohi
T
T
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D005453:Fluorescence; D016257:Fura-2; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis / Q000097:blood; D008564:Membrane Potentials / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D037342:Pertussis Toxin; D011760:Pyrrolidinones / Q000494:pharmacology; D013268:Stimulation, Chemical; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004963:Estrenes; D006893:Hydroxyeicosatetraenoic Acids; D011760:Pyrrolidinones; D010566:Virulence Factors, Bordetella; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015544:Inositol 1,4,5-Trisphosphate; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2