Paradoxical effects of colchicine on the activation of human neutrophilis by chemotactic factors and inflammatory microcrystal.
Neutrophil activation by chemotactic factors and by inflammatory microcrystals is accompanied by increases in protein tyrosine phosphorylation and by the activation of the NADPH oxidase. The addition of colchicine inhibited both responses induced by triclinic monosodium urate or calcium pyrophosphate crystals. On the other hand, colchicine enhanced the tyrosine phosphorylation of specific protein in neutrophils stimulated by chemotactic factor and augmented the production of superoxide anions induced by these same agonists. The effects of colchicine were shared by other anti-microtubule agents (nocodazole and vinblastine) but not by its inactive analogue beta-lumicolchicine, trimethylcolchicinic acid, indomethacin, or phenylbutazone. Furthermore, the (enhancing as well as inhibitory) effects of colchicine on tyrosine phosphorylation and superoxide anion production were reversed by taxol. Finally, in human cytoplasts colchicine again inhibited microcrystal-stimulated tyrosine phosphorylation but did not change chemotactic factor-stimulated phosphorylation. These data strongly support the hypothesis that microtubule-related mechanisms are involved in the modulation of the tyrosine phosphorylation response in human neutrophils, and suggest that a relationship may exist between the augmentation of tyrosine phosphorylation and of the stimulation of the NADPH oxidase induced by chemotactic factors.
Roberge
C J
CJ
Centre de Recherche en Rhumatologie et Immunologie, Faculty of Medicine, Université Laval, Sainte-Foy, Québec, Canada.
Gaudry
M
M
Gilbert
C
C
Malawista
S E
SE
de Médicis
R
R
Lussier
A
A
Poubelle
P E
PE
Naccache
P H
PH
D000328:Adult; D002131:Calcium Pyrophosphate / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism; D014527:Uric Acid / Q000494:pharmacology
D014527:Uric Acid; D014443:Tyrosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D017239:Paclitaxel; D003078:Colchicine; D002131:Calcium Pyrophosphate