Mechanism of action of colchicine in acute urate crystal-induced arthritis.
Phagocytosis of urate crystals by human or rabbit neutrophils induces the synthesis and release of a glycoprotein, the crystal-induced chemotactic factor (CCF), which is chemotactically active both in vitro and in vivo. It has been proposed that CCF is a prime mediator of the acute gouty attack. Colchicine has been shown to decrease the production and release of this factor in vitro. In these studies, colchicine, at nonleukopenic doses, is shown to abrogate the acute arthritis induced by monosodium urate crystals in rabbits, but to have no effect upon the arthritis induced by the injection of the purified cell-derived chemotactic factor. Serum colchicine levels were 0.48-0.58 muM at 30 min and 0.12-0.3 muM at 90 min after intravenous injection of 0.2 mg/kg colchicine. Peripheral blood polymorphonuclear leukocytes obtained from colchicine-treated animals migrated normally towards a chemotactic stimulus but failed to produce CCF after phagocytosis of monosodium urate crystals. The dialyzed synovial fluid from rabbits injected with microcrystalline sodium urate contained chemotactic activity that was not present when animals were also given intravenous colchicine or injected intra-articularly with the chemotactic factor formyl-methionyl-leucyl-phenylalanine. Furthermore, the synovial fluid from rabbits injected with microcrystalline sodium urate significantly decreased (125)I-CCF binding to neutrophils. The binding of (125)I-CCF to its neutrophil receptor was not significantly reduced by the synovial fluid of colchicine-treated rabbits nor by the synovial fluid of control rabbits injected with the chemotactic factor formyl-methionyl-leucyl-phenylalanine. Colchicine (10 and 0.1 muM) was shown to have no effect upon the binding of (125)I-CCF to its cell receptor.
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003078:Colchicine / Q000097:blood / Q000494:pharmacology*; D005260:Female; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits; D013582:Synovial Fluid / Q000502:physiology; D014527:Uric Acid
D014527:Uric Acid; D003078:Colchicine