Apolipoprotein (apo) E inhibits the capacity of monosodium urate crystals to stimulate neutrophils. Characterization of intraarticular apo E and demonstration of apo E binding to urate crystals in vivo.
Factors that modulate the ability of monosodium urate crystals to stimulate leukocytes could regulate gouty inflammation. Lipoproteins that bear apo B-100 and apo E bind to urate crystals and suppress crystal-neutrophil interaction. In this study, we observed that urate crystals, coated with apo E of monocyte origin, had a diminished ability to stimulate neutrophils. Apo E was also detected on the surface of urate crystals recovered from gout patients. Thus, we analyzed apo E in noninflammatory synovial fluid, and found it to be associated with particles of heterogeneous size and of predominantly alpha and pre-beta electrophoretic mobility. Local articular synthesis of at least a portion of synovial fluid apo E was suggested because (a) the synovial fluid/plasma concentration ratio of apo E was significantly higher than that for both apo B and apo A-I, which are not widely synthesized by extrahepatic tissues, (b) cultured rheumatoid synovial cells in first passage secreted apo E, (c) a portion of synovial fluid apo E was heavily sialylated. We conclude that synovial fluids contain apo E that appears partly of local origin. Apo E binds to urate crystals and could modulate gouty inflammation.
Terkeltaub
R A
RA
San Diego Veterans Administration Medical Center, CA 92161.
Dyer
C A
CA
Martin
J
J
Curtiss
L K
LK
D001057:Apolipoproteins E / Q000378:metabolism / Q000502:physiology*; D002356:Cartilage / Q000378:metabolism; D003460:Crystallization; D006073:Gout / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013582:Synovial Fluid / Q000737:chemistry*; D014527:Uric Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001057:Apolipoproteins E; D014527:Uric Acid