Potentiation and inhibition of migration of human neutrophils by auranofin.
OBJECTIVE
As auranofin resembles some neutrophil activating sulphur containing compounds, it was decided to investigate whether it had activating effects on neutrophil migration in addition to the published inhibitory effects.


METHODS
The Boyden chamber assay was used to determine the migration velocity of human neutrophils. The difference between chemotaxis and chemokinesis was established with a chequerboard assay.


RESULTS
Low concentrations of auranofin stimulated human neutrophil migration; concentrations of auranofin higher than 1 mumol/l were inhibitory. Inhibitors of leukotriene formation, or of protein kinase C, had the same effect on auranofin induced potentiation of migration as on fMLP activated migration. Auranofin, at a concentration of 100 nmol/l, caused a transient increase in the cGMP level of neutrophils. The auranofin induced increase in migration was strongly inhibited by methylene blue and by LY83583, two inhibitors of cGMP accumulation.


CONCLUSIONS
The auranofin induced enhancement of migration is partly due to a chemokinetic effect, but mainly due to a chemotactic effect. The potentiating effect of auranofin on migration is not specifically due to the ability of the drug to inhibit protein kinase C activity or to generate leukotrienes. These results suggest that the enhancement of neutrophil migration by low levels of auranofin is related to the enhancement of cGMP levels in neutrophils.
Elferink
J G
JG
Department of Medical Biochemistry, University of Leiden, The Netherlands.
de Koster
B M
BM
D000634:Aminoquinolines / Q000494:pharmacology; D001310:Auranofin / Q000494:pharmacology*; D002464:Cell Migration Inhibition; D002633:Chemotaxis; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors
D000634:Aminoquinolines; D007975:Leukotriene B4; D001310:Auranofin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C041715:6-anilino-5,8-quinolinedione; D011493:Protein Kinase C; D006152:Cyclic GMP