[Inhibitory effects of exogenous eicosapentaenoic acid on generation of leukotriene C4 and leukotriene B4 by human leukocytes stimulated with calcium ionophore].
Effects of exogenous eicosapentaenoic acid (EPA) and arachiodonic acid (AA) on generation of leukotriences C4, C5, B4 and B5 were assessed in human leukocytes stimulated with calcium ionophore A23187. Human leukocytes were obtained from healthy volunteers using the dextran sedimentation of peripheral blood and stimulated with 1 microgram/ml calcium ionophore A23187 in the absence or presence of EPA (1-30 micrograms/ml) and/or AA (1-30 micrograms/ml). Leukotriences from leukocytes samples were separated and quantitated by reverse phase high performance liquid chromatography. Mean generation of LTC4 in the absence of fatty acid was 78.2 +/- 25.4 ng/10(7) cells (Mean +/- SD, n = 6). In the presence of EPA, the generation of LTC4 increased a little but significant (p < 0.05) to 85.3 +/- 24.2 ng/10(7) cells at low dose (1 microgram/ml) of EPA, and then decreased to 39.7 +/- 23.4 ng/10(7) cells at high dose (30 micrograms/ml) of EPA (p < 0.05). LTB4 generation was 213.2 +/- 38.0 ng/10(7) cells without fatty acids, and decreased to 174.0 +/- 48.0 ng/10(7) cells at 30 micrograms/ml EPA (p < 0.05). LTC5 and LTB5 production were detectable at 1 microgram/ml EPA and reached to maximum at 10 micrograms/ml EPA with 21.9 +/- 15.6 ng/10(7) cells and 21.8 +/- 7.1 ng/10(7) cells, respectively. Total LTC (LTC4 + LTC5) generation with high dose of EPA (57.2 +/- 28.0 ng/10(7) cells) decreased significantly compared with that in the absence of fatty acids (78.2 +/- 25.4 ng/10(7) cells). At 10 micrograms/ml of AA, both LTC4 and LTB4 generation significantly increased to 114.2 +/- 5.3% and 129.0 +/- 9.5% of control, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Sakakibara
H
H
Department of Internal Medicine, School of Medicine, Fujita Health University.
Hirose
K
K
Matsushita
K
K
Nakamura
S
S
Sato
M
M
Kako
K
K
Suetsugu
S
S
D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D017997:Leukotriene C4 / Q000378:metabolism*; D008297:Male
D007975:Leukotriene B4; D016718:Arachidonic Acid; D017997:Leukotriene C4; D000001:Calcimycin; D015118:Eicosapentaenoic Acid