Inhibition of human neutrophils by auranofin: chemotaxis and metabolism of arachidonate via the 5-lipoxygenase pathway
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Inhibition of human neutrophils by auranofin : chemotaxis and metabolism of arachidonate via the 5-lipoxygenase pathway. / Elmgreen, J; Ahnfelt-Rønne, I; Nielsen, O H.
In: Annals of the Rheumatic Diseases, Vol. 48, No. 2, 02.1989, p. 134-8.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Inhibition of human neutrophils by auranofin
T2 - chemotaxis and metabolism of arachidonate via the 5-lipoxygenase pathway
AU - Elmgreen, J
AU - Ahnfelt-Rønne, I
AU - Nielsen, O H
PY - 1989/2
Y1 - 1989/2
N2 - The effect of auranofin on human neutrophil (PMN) 5-lipoxygenase activity and leucotriene B4 (LTB4) chemotaxis was investigated. [1-14C]Arachidonic acid was incorporated into the purified cells until steady state conditions were obtained. After preincubations with serial dilutions of auranofin arachidonic acid release and metabolism were stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thin layer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxis of PMNs towards LTB4 was measured in a modified Boyden chamber. Auranofin showed dose dependent inhibition of both the 5-lipoxygenase pathway (IC50 17.4 X 10(-6) mol/l) and of chemotaxis (IC50 45 X 10(-6) mol/l). The release of arachidonic acid from phospholipids was unaffected in the concentration range tested (1-1000 mumol/l). Inhibition of both neutrophil motility and cellular synthesis of proinflammatory eicosanoids may thus contribute to the beneficial clinical effects of auranofin in rheumatoid arthritis.
AB - The effect of auranofin on human neutrophil (PMN) 5-lipoxygenase activity and leucotriene B4 (LTB4) chemotaxis was investigated. [1-14C]Arachidonic acid was incorporated into the purified cells until steady state conditions were obtained. After preincubations with serial dilutions of auranofin arachidonic acid release and metabolism were stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thin layer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxis of PMNs towards LTB4 was measured in a modified Boyden chamber. Auranofin showed dose dependent inhibition of both the 5-lipoxygenase pathway (IC50 17.4 X 10(-6) mol/l) and of chemotaxis (IC50 45 X 10(-6) mol/l). The release of arachidonic acid from phospholipids was unaffected in the concentration range tested (1-1000 mumol/l). Inhibition of both neutrophil motility and cellular synthesis of proinflammatory eicosanoids may thus contribute to the beneficial clinical effects of auranofin in rheumatoid arthritis.
KW - Arachidonate 5-Lipoxygenase/blood
KW - Arachidonic Acid
KW - Arachidonic Acids/blood
KW - Auranofin/pharmacology
KW - Cells, Cultured
KW - Chemotaxis, Leukocyte/drug effects
KW - Humans
KW - Leukotriene B4/blood
KW - Lipoxygenase Inhibitors
KW - Neutrophils/drug effects
U2 - 10.1136/ard.48.2.134
DO - 10.1136/ard.48.2.134
M3 - Journal article
C2 - 2539060
VL - 48
SP - 134
EP - 138
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 2
ER -
ID: 218728646