Complexation of iron cation by sodium urate crystals and gouty inflammation.
Gouty inflammation can be suppressed by an iron chelator. We therefore hypothesized that arthritis associated with sodium urate crystal deposition could follow the incomplete complexation of iron cation with subsequent oxidant generation as the metal cycles through reduced and oxidized states. Urate crystals adsorbed Fe3+ in vitro and crystals collected from a human tophus had significant concentrations of ionizable iron. Urate crystals oxidized deoxyribose to a thiobarbituric acid (TBA)-reactive product, augmented luminol chemiluminescence by neutrophils, released leukotriene B4 from neutrophils, activated complement, and promoted neutrophil chemotaxis. All of these events increased with the concentration of complexed iron and were suppressed by the iron chelator deferoxamine or the .OH scavenger dimethylthiourea. These results suggest that some portion of gouty inflammation after urate crystal deposition could result from the incomplete complexation of iron with subsequent catalytic generation of reactive oxygen species.
Ghio
A J
AJ
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Kennedy
T P
TP
Rao
G
G
Cooke
C L
CL
Miller
M J
MJ
Hoidal
J R
JR
D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002712:Chlorides; D003167:Complement Activation / Q000187:drug effects; D003460:Crystallization; D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry; D006073:Gout / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D007975:Leukotriene B4 / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D014527:Uric Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D002712:Chlorides; D005290:Ferric Compounds; D007975:Leukotriene B4; D014527:Uric Acid; D007501:Iron; D003676:Deferoxamine; C024555:ferric chloride