Enhanced superoxide generation and the decreased superoxide scavenging activity of peripheral blood leukocytes in Behçet's disease--effects of colchicine.
Enhanced superoxide radical (O2-) generation by polymorphonuclear cells (PMN) has been suggested to mediate tissue damage associated with Behçet's disease (BD). Because superoxide dismutase (SOD) provides protection from O2- we investigated whether the superoxide scavenging activity (SSA) of PMN, mononuclear cells (MNC) or plasma has a correlation to the amount of O2- generated by PMN in BD. We also studied the effects of colchicine, a potent inhibitor of phagocytosis, on the SSA of PMN. In BD, O2- release by both non-stimulated PMN and those stimulated with opsonized zymosan (OZ), or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), was enhanced. The SSA of PMN, but not MNC and plasma, was significantly lower in BD patients as compared with healthy controls. The SSA of PMN showed a strong negative correlation with their O2- release. The SSA of PMN was lower in the BD patients with elevated erythrocyte sedimentation rates and C-reactive protein levels than in those with normal test results. In addition, we found that colchicine treatment increased the SSA of PMN toward normal levels in BD patients. In vitro studies demonstrated that the SSA in PMN obtained from healthy adults was decreased after stimulation with either OZ or PMA. Colchicine could prevent the decrease in the SSA when PMN were stimulated with OZ, but not when stimulated with PMA. Our results suggest that the enhanced O2- release by PMN in vivo may be responsible for the decreased SSA of PMN in BD and the PMN might be able to release more O2- in tissues. Colchicine may increase the SSA of PMN toward normal levels by blocking phagocytosis.
Pronai
L
L
Fourth Department of Internal Medicine, Tokai University School of Medicine, Kanagawa-ken, Japan.
Ichikawa
Y
Y
Nakazawa
H
H
Arimori
S
S
D000328:Adult; D001528:Behcet Syndrome / Q000097:blood / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D016166:Free Radical Scavengers; D013481:Superoxides; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate; D003078:Colchicine