The inflammatory response to intraarticular urate crystals is known to be variable in gouty arthritis. One source of variability may be the modulation of cellular responses by crystal-bound proteins. We have identified three apolipoproteins among the polypeptides bound to urate crystals exposed to plasma. Identification was first based on their coelectrophoresis with polypeptides from isolated lipoproteins and diminution in the protein coat of crystals exposed to lipoprotein-depleted plasma. The apoproteins were immunochemically identified by the Western blotting technique as apoprotein A-I, apoprotein B (apo B), and apoprotein E. Because neutrophils play a central role in acute gout, we investigated the potential effects of lipoproteins on neutrophil-urate crystal interactions. Plasma profoundly inhibited urate crystal-induced neutrophil luminol-dependent chemiluminescence (CL). Lipoprotein depletion by KBr density gradient centrifugation completely abrogated the inhibitory effect of plasma on urate-induced CL. The inhibitory activity of lipoprotein-depleted plasma was restored by adding back the d less than or equal to 1.25 g/cm3 lipoprotein fraction. Plasma also inhibited urate crystal-induced neutrophil superoxide generation and cytolysis (lactic dehydrogenase loss). This inhibition was significantly diminished by lipoprotein depletion, indicating that the lipoprotein effect was not limited to CL. Lipoprotein-depleted plasma reconstituted with very low, intermediate, and low density lipoproteins (LDL) inhibited crystal-induced CL. High density lipoprotein reconstitution was without effect. Immunodepletion from plasma of all apo B lipoproteins by agarose-bound apo B-specific antibody also removed all inhibitory activity for urate-induced CL. Thus, apo B lipoproteins were shown to be the inhibitory species in plasma. Binding of apo B lipoproteins to urate crystals and inhibition of CL was also seen in the absence of other plasma proteins. In addition, the binding of whole lipoprotein particles to the crystals was verified by detection of crystal-associated cholesterol in addition to the apoprotein. The effects of LDL on urate crystal-induced CL were stimulus specific. Coincubation of urate crystals and neutrophils in the presence of 10 micrograms/ml LDL resulted in 83% inhibition. In contrast, CL responses to a chemotactic hexapeptide, opsonized zymosan, and Staphylococcus aureus were not inhibited by LDL. The effects of depletion of apo B lipoproteins on plasma suppression of urate crystal-induced CL appeared to be unique. Plasma or sera depleted of other urate crystal-binding proteins including fibrinogen, fibronectin, C1q, and IgG retained virtually all their CL inhibitory activity. Lipoproteins containing apo B are thus a major regulator of neutrophil responses to urate crystals. These lipoproteins are present in variable concentration in synovial fluid and may exert an important influence on the course of gout.
R Terkeltaub, L K Curtiss, A J Tenner, M H Ginsberg
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Arthritis & Rheumatism | 2006 |
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Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation
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Arthritis & Rheumatism | 2005 |
Gout in Solid Organ Transplantation: A Challenging Clinical Problem
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Drugs | 2005 |
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EMC - Aparato Locomotor | 2003 |
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RC Landis, DR Yagnik, O Florey, P Philippidis, V Emons, JC Mason, DO Haskard |
Arthritis & Rheumatism | 2002 |
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Biomaterials | 2000 |
Silica Binds Serum Proteins Resulting in a Shift of the Dose-Response for Silica-Induced Chemokine Expression in an Alveolar Type II Cell Line
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Toxicology and Applied Pharmacology | 1999 |
Effects of Human Low-Density Lipoproteins on Superoxide Production by Formyl-Methionyl-Leucyl-Phenylalanine Activated Polymorphonuclear Leukocytes
C Bonneau, R Couderc, M Tissot, A Athias, M Roch-Arveiller, JP Giroud |
Clinical Chemistry and Laboratory Medicine | 1997 |
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Digestive Diseases and Sciences | 1997 |
The interaction of monoclinic calcium pyrophosphate dihydrate crystals with neutrophils
CI Winternitz, JK Jackson, HM Burt |
Rheumatology International | 1996 |
Triglyceride-rich lipoproteins improve survival when given after endotoxin in rats
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Journal of Experimental Medicine | 1995 |
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Annals of the rheumatic diseases | 1995 |
Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death
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Journal of Clinical Investigation | 1993 |
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Annals of the rheumatic diseases | 1993 |
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Scandinavian Journal of Rheumatology | 1992 |
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JS Flier, LH Underhill, C Grunfeld, KR Feingold |
New England Journal of Medicine | 1992 |
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
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Journal of Clinical Investigation | 1991 |
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R Terkeltaub, C Zachariae, D Santoro, J Martin, P Peveri, K Matsushima |
Arthritis & Rheumatism | 1991 |
Tophus-derived monosodium urate monohydrate crystals are biologically much more active than synthetic counterpart
A Stanković, P Front, A Barbara, DR Mitrović |
Rheumatology International | 1991 |
Crystal-induced neutrophil activation. I. Initiation and modulation of calcium mobilization and superoxide production by microcrystals
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Arthritis & Rheumatism | 1991 |
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FEBS Letters | 1991 |
Urate Deposition in Man and its Clinical Consequences
U Gresser, N Zöllner |
1991 | |
The effects of γ-interferon on human peripheral blood monocyte/macrophage-mediated bone particle degradation
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Bone and Mineral | 1990 |
Hyperurikämie, Gicht und andere Störungen des Purinhaushalts
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Lipid Modulators of Cell Function
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Nutrition Reviews | 1989 |
Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma
DM Stafforini, ME Carter, GA Zimmerman, TM McIntyre, SM Prescott |
Proceedings of the National Academy of Sciences | 1989 |
Serum and plasma inhibit neutrophil stimulation by hydroxyapatite crystals. evidence that serum αl2-hs glycoprotein is a potent and specific crystal-bound inhibitor
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Arthritis & Rheumatism | 1988 |
Crystal-Associated Arthropathies
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Clinics in Geriatric Medicine | 1988 |
The Inflammatory Reaction to Crystals
RA Terkeltaub, MH Ginsberg |
Rheumatic diseases clinics of North America | 1988 |
Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty tophi and rheumatoid nodules
DG Palmer, N Hogg, I Denholm, CA Allen, J Highton, PA Hessian |
Rheumatology International | 1987 |
Low density lipoprotein inhibits the physical interaction of phlogistic crystals and inflammatory cells
R Terkeltaub, D Smeltzer, LK Curtiss, MH Ginsberg |
Arthritis & Rheumatism | 1986 |
Preliminary evidence for the presence of an inhibitor on the surface of natural monosodium urate crystals
TP Gordon, PJ Roberts-Thomson |
Arthritis & Rheumatism | 1986 |
Products of polymorphonuclear cell injury inhibit IgG enhancement of monosodium urate-induced superoxide production
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Arthritis & Rheumatism | 1986 |
Lack of correlation between in vitro and in vivo effects of low density lipoprotein on the inflammatory activity of monosodium urate crystals
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Annals of the rheumatic diseases | 1986 |
Apolipoprotein B mediates the capacity of low density lipoprotein to suppress neutrophil stimulation by particulates
R Terkeltaub, J Martin, LK Curtiss, MH Ginsberg |
The Journal of biological chemistry | 1986 |
Immunology of Rheumatic Diseases
S Gupta, N Talal |
1985 | |
Studies on the interaction of rheumatoid factor with monosodium urate crystals and case report of coexistent tophaceous gout and rheumatoid arthritis
TP Gordon, MJ Ahern, C Reid, PJ Roberts-Thomson |
Annals of the rheumatic diseases | 1985 |
Calcinosis of joints and periarticular tissues associated with vitamin D intoxication
RC Butler, PA Dieppe, AC Keat |
Annals of the rheumatic diseases | 1985 |