Oxidative cross-linking of immune complexes by human polymorphonuclear leukocytes.

Jasin, Hugo E.

doi:10.1172/jci113310

Cited by 49 publications

(19 citation statements)

References 46 publications

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“…This mechanism has similarities to other oxidant systems that cause red cell lysis : photooxidation of protoporphyrin also causes protein cross-linking and clustering of the membrane proteins that is closely associated with lysis [42,43]. Protein cross-linking by HOCl has been reported previously [44][45][46] and our results with globin demonstrate that a substantial amount of dimerization occurred even at a 1 : 1 ratio of oxidant to protein. This is surprising in view of the number of potentially reactive amino acids [13], and indicates that this is a major reaction of HOCl and HOBr.…”

Section: Discussionsupporting

confidence: 82%

Comparison of human red cell lysis by hypochlorous and hypobromous acids: insights into the mechanism of lysis

Vissers

Carr

Chapman

1998

Biochemical Journal

103

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Human red blood cells are lysed by the neutrophil-derived oxidant hypochlorous acid (HOCl), although the mechanism of lysis is unknown. Hypobromous acid (HOBr), a similarly reactive oxidant, lysed red cells approx. 10-fold faster than HOCl. Therefore we compared the effects of these oxidants on thiols, membrane lipids and proteins to determine which reactions are associated with lysis. There was no difference in the loss of reduced glutathione or membrane thiols with either oxidant, but HOBr reacted more readily with membrane lipids and proteins. Bromohydrin derivatives of phospholipids and cholesterol were seen at approx. one-tenth the level of oxidant than chlorohydrins were. However, these products were detected only with high concentrations of HOCl or HOBr, which caused instant haemolysis. Membrane protein modification occurred at much lower doses of oxidant and was more closely correlated with lysis. SDS/PAGE analysis showed that band 3, the anion transport protein, was lost at the lowest dose of HOBr and at the higher concentrations of HOCl. Labelling the red cells with eosin 5-maleimide, a fluorescent label for band 3, suggested possible clustering of this protein in oxidant-exposed cells. There was also irreversible cross-linking of all the major membrane proteins; this reaction occurred more readily with HOBr. The results indicate that membrane protein modification is the reaction responsible for HOCl-mediated lysis. These effects, and particularly cross-link formation, might result in clustering of band 3 and other membrane and cytoskeletal proteins to form haemolytic pores.

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Section: Discussionsupporting

confidence: 82%

Comparison of human red cell lysis by hypochlorous and hypobromous acids: insights into the mechanism of lysis

Vissers

Carr

Chapman

1998

Biochemical Journal

103

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“…Work in our laboratory had shown that in vitro oxidative attack on IgG resulted in the generation of covalent cross-linked aggregates that behaved as immunocomplexes in that they were able to activate the complement system and precipitate with rheumatoid factor (5). Further work showed that activated human PMN or monocytes induced similar changes in native IgG and that generation of HOCl by these cells was responsible for cross-linking (4,18). Finally, analysis of IgG obtained from inflammatory synovial fluids showed evidence of covalent cross-linking and oxidative modification (6).…”

Section: Discussionmentioning

confidence: 94%

“…It should be pointed out that the present experiments were designed to distinguish the effects of the chemical modification of the IgGs from the proinflammatory effects resulting from intermolecular cross-linking and aggregation. In the experiments conducted to gauge IgG binding to the FcR, for instance, it was important to use purified monomers, because the cooperativity effects of two or more binding domains in close proximity may increase the apparent binding affinity by as much as 10 4 .…”

Section: Discussionmentioning

confidence: 99%

“…Herein, we examine the biologic effects of exposure of IgG to hypochlorous acid (HOCl) and peroxynitrite (ONOO) A ctivation of phagocytic cells by immune complexes or cytokines within the inflamed joint gives rise to large amounts of highly reactive oxygen-derived products that in conjunction with cell peroxidases, free divalent metals, halide ions, and other substrates play a major role in the generation of tissue injury in acute and chronic inflammatory reactions (1)(2)(3). We have previously shown that activation of inflammatory cells resulting in the production of hypochlorous acid (HOCl), 3 the end product of superoxide ion, mediates covalent cross-linking of IgG in vitro (4). The modified IgG aggregates were shown to have characteristics similar to true immunocomplexes in that they interacted with rheumatoid factor and C1q (5).…”

Section: Inflammatory Properties Of Igg Modified By Oxygen Radicals Amentioning

confidence: 99%

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Inflammatory Properties of IgG Modified by Oxygen Radicals and Peroxynitrite

Uesugi

Yoshida

Jasin

2000

The Journal of Immunology

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In inflammatory arthritis, there is evidence indicating that the affected tissues produce large amounts of oxygen-free radicals and NO. Herein, we examine the biologic effects of exposure of IgG to hypochlorous acid (HOCl) and peroxynitrite (ONOO). The concentrations of IgG modified by chlorination and nitrosation were measured in synovial fluids from inflammatory and noninflammatory arthritis. Human IgG was exposed to increasing concentrations of HOCl and ONOO, and the resulting products were tested for complement component binding; binding to FcγRI; activation of polymorphonuclear neutrophils; effect on the Ab-combining site of Abs; and in vivo inflammatory activity in a rabbit model of acute arthritis. Rheumatoid synovial fluids contained significantly greater concentrations of nitrosated and chlorinated IgG compared with ostearthritic specimens. In vitro exposure of human IgG to HOCl and ONOO resulted in a concentration-dependent decrease in C3 and C1q fixation. The decrease in Fc domain-dependent biologic functions was confirmed by competitive binding studies to the FcγRI of U937 cells. HOCl-treated IgG monomer was 10 times less effective in competing for binding compared with native IgG, and ONOO-treated IgG was 2.5 times less effective. The modified IgGs were also ineffective in inducing synthesis of H2O2 by human PMN. The Ag-binding domains of IgG also showed a concentration-dependent decrease in binding to Ag. The ability of the modified IgGs to induce acute inflammation in rabbit knees decreased 20-fold as gauged by the intensity of the inflammatory cell exudates. These studies clarify the modulating role of biological oxidants in inflammatory processes in which Ag-autoantibody reactions and immune complex pathogenesis may play an important role.

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“…Over the last 25 years, a variety of mono-functional and hetero-bifunctional reagents have been developed that target different side chains of proteins for coupling. Crosslinkers with reaction chemistries such as photoactivatable molecules [30], fluorescent linkers [31], cleavable linkers [32], antibody-antigen complexes [33], metal complexes [34], and biotin-streptavidin complexes [31,35] have been reported for protein couplings. However, few crosslinking methods possess properties such as good reaction specificity, high product yields, limited side reactions and ability to account the crosslinking efficiency [31,35].…”

Section: Introductionmentioning

confidence: 99%

Crosslinking of viral nanoparticles with “clickable” fluorescent crosslinkers at the interface

et al. 2010

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Cu (I) catalyzed alkyne-azide cycloaddition (CuAAC) reaction, a typical "click" reaction, is one of the modular synthetic approaches which has been broadly used in various organic syntheses, medicinal chemistry, materials development and bioconjugation applications. We have for the first time synthesized two dialkyne derivatized fluorescent crosslinkers which could be applied to crosslink two biomolecules using CuAAC reaction. Turnip yellow mosaic virus, a plant virus with unique structural and chemical properties, was used as a prototypical scaffold to form a 2D single layer at the interface of two immiscible liquids and crosslinked with these two linkers by the CuAAC reaction. Upon crosslinking, the fluorescence of both linkers diminished, likely due to the distortion of the polymethylene backbone, which therefore could be used to indicate the completion of the reaction.

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Oxidative cross-linking of immune complexes by human polymorphonuclear leukocytes.

Cited by 49 publications

References 46 publications

Comparison of human red cell lysis by hypochlorous and hypobromous acids: insights into the mechanism of lysis

Comparison of human red cell lysis by hypochlorous and hypobromous acids: insights into the mechanism of lysis

Inflammatory Properties of IgG Modified by Oxygen Radicals and Peroxynitrite

Crosslinking of viral nanoparticles with “clickable” fluorescent crosslinkers at the interface

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