Oxidative modification of ovalbumin.

Olszowski, S.; Olszowska, Ewa; Stelmaszyńska, Teresa; Krawczyk, Agnieszka; Marcinkiewicz, Janusz; Baczek, N

doi:10.18388/abp.1996_4462

Cited by 27 publications

(15 citation statements)

References 24 publications

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“…HPLC analysis of chlorinated OVA which was performed prior to DTT reduction demonstrated that chlorinated OVA (2-4.5 mmol of HOCl/mg OVA) existed mainly as a monomeric protein with a molecular mass close to that of native OVA. At HOCl concentrations higher than 2.5 mmol/mg, OVA became a partially unfolded molecule [6]. Thus, our result indicates a similar chlorination of RSA as previously reported for OVA.…”

Section: Rsa Can Be Modified By Chlorinationsupporting

confidence: 90%

Alteration of an Autoantigen by Chlorination, a Process Occurring During Inflammation, Can Overcome Adaptive Immune Tolerance

Westman

Harris

2004

Scand J Immunol

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Autoimmune diseases are characterized by chronic inflammation in target organs and immunoreactivity towards one or multiple autoantigens. Several potential mechanisms of tolerance breaking have been postulated, one being inflammationassociated events. We have investigated whether chlorination of an autoantigen can lead to disruption of self-tolerance. Chlorination of antigens might occur during inflammation via the granulocyte-specific, myeloperoxidase-catalysed conversion of hydrogen peroxide to hypochlorous acid (HOCl). HOCl, being a strong oxidant, reacts with proteins both within cellular phagosomes and in the immediate extracellular environment. By immunizing Lew.1AV1 rats with chlorinated or unmodified rat serum albumin (RSA), we could detect tolerance-breaking effects of chlorination. RSA is a systemic autoantigen in rat not inducing antibody production upon immunization in its unmodified form. Rats immunized with chlorinated RSA (RSA-Cl) developed high titres of immunoglobulin G (IgG) specific for RSA-Cl which cross-reacted with native RSA. T cells reactive with both RSA-Cl and RSA were detected by [ 3 H]-thymidine incorporation. We hence speculated that immunological tolerance established for unmodified proteins, during certain circumstances such as inflammation, might be broken by induced protein chlorination. T cells specific for the chlorinated protein can confer help to B cells recognizing both the chlorinated and the native form of the protein, leading to the formation of high-affinity autoreactive antibodies and possibly autoimmune disease.

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Section: Rsa Can Be Modified By Chlorinationsupporting

confidence: 90%

Alteration of an Autoantigen by Chlorination, a Process Occurring During Inflammation, Can Overcome Adaptive Immune Tolerance

Westman

Harris

2004

Scand J Immunol

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“…Chlorination of CII was detected as an increase in high molecular weight bands, which are due probably to chlorination of tyrosine and lysine residues in the collagen molecule. It has been reported previously that chlorination of lysine residues in low density lipoproteins (LDL) resulted in increased aggregation of this protein [20] and has similarly increased aggregation of ovalbumin (OVA), reported as a consequence of chlorination [21]. Thus, our results indicate a similar chlorination of RCII as reported previously for LDL and OVA.…”

Section: Chlorination Of Rat Collagen IIsupporting

confidence: 89%

Arthritogenicity of collagen type II is increased by chlorination

Westman

Lundberg

Harris

2006

Clinical and Experimental Immunology

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SummaryDuring inflammation, activated neutrophils, monocytes and macrophages produce and release myeloperoxidase (MPO). MPO converts hydrogen peroxide to hypochlorous acid, a highly reactive and oxidizing agent. Proteins subjected to hypochlorous acid become chlorinated. We analysed how chlorination of the cartilage antigen collagen type II (CII) affects its immunogenic and arthritogenic properties by studying immune responses to chlorinated CII in comparison to immune responses to CII and by studying the development of arthritis in rats immunized with CII-Cl. CII-Cl immunization of LEW.1AV1 rats caused a 100% incidence of arthritis with a mean maximum score of 9·2 (maximal score possible 16). The same dose of non-chlorinated CII did not induce arthritis at all. Rats immunized with CII-Cl developed high anti-CII-Cl IgG titres and also developed IgG antibodies recognizing the non-chlorinated form of CII. Analysis of cytokine mRNA expression in lymph nodes 10 days after immunzation revealed an increased expression of interferon (IFN)-γ γ γ γ mRNA and interleukin (IL)-1 β β β β mRNA in CII-Cl-immunized rats compared to CII-immunized rats. Thus, chlorination of CII increased its immunogenicity as well as its arthritogenicity. As neutrophils, monocytes and macrophages are abundant cells in arthritic joints of patients with rheumatoid arthritis, chlorination might be a mechanism by which immunoreactivity to CII is induced and by which chronic joint inflammation is supported.

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“…It is widely known that protein chlorination results in modification of reactive amino-acid side chains containing such functional groups as: -SH, -SS-, RSR, -NH 2 , OH (in Tyr) or indole (in Trp) (Hampton et al, 1998). Chlorination of collagen II with HOCl/OClleads to the conversion of tyrosine to dichlorotyrosine as it was observed for other proteins (Kettle, 1996;Olszowski et al, 1996). As shown in Table 1 dichlorotyrosine formation could be eas-ily traced as absorbance increase at 305-308 nm in the difference spectra of chlorinated CII.…”

Section: Resultsmentioning

confidence: 87%

“…As suggested by the HPLC, SDS/PAGE and CD data, hypochlorite chlorination was followed by CII fragmentation even at low hypochlorite concentrations (less than 1 mM). Unlike in the case of albumin (Olszowski et al, 1996) and fibronectin (Vissers & Winterbourn, 1991), for collagen this tendency seems to prevail over aggregation. The degree of CII fragmentation evaluated from CD measurements was very similar to that calculated from experiments with tritium labelled type II bovine articular collagen (Davies et al, 1993).…”

Section: Discussionmentioning

confidence: 93%

Collagen type II modification by hypochlorite.

Olszowski

Mak²,

Olszowska³

et al. 2003

Acta Biochim Pol

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Oxidation of proteins is a common phenomenon in the inflammatory process mediated by highly reactive agents such as hypochlorite (HOCl/OCl(-)) produced by activated neutrophils. For instance, in rheumatoid arthritis hypochlorite plays an important role in joint destruction. One of the major targets for HOCl/OCl(-) is collagen type II (CII) - the primary cartilage protein. In our study, HOCl/OCl(-) mediated collagen II modifications were tested using various methods: circular dichroism (CD), HPLC, ELISA, dynamic light scattering (DLS), fluorimetry and spectrophotometry. It was shown that hypochlorite action causes deamination with consecutive carbonyl group formation and transformation of tyrosine residues to dichlorotyrosine. Moreover, it was shown that ammonium chloramine (NH(2)Cl) formed in the reaction mixture reacts with CII. However, in this case the yield of carbonyl groups and dichlorotyrosine is lower than that observed for HOCl/OCl(-) by 50%. CD data revealed that collagen II exists as a random coil in the samples and that chlorination is followed by CII fragmentation. In the range of low HOCl/OCl(-) concentrations (up to 1 mM) 10-90 kDa peptides are predominant whereas massive production of shorter peptides was observed for high (5 mM) hypochlorite concentration. DLS measurements showed that chlorination with HOCl/OCl(-) decreases the radius of collagen II aggregates from 30 to 6.8 nm. Taking into account the fact that chlorinated collagen is partially degraded, the DLS results suggest that smaller micelles are formed of the 10-90 kDa peptide fraction. Moreover, collagen chlorination results in epitope modification which affects CII recognition by anti-CII antibodies. Finally, since in the synovial fluid the plausible hypochlorite concentration is smaller than that used in the model the change of size of molecular aggregates seems to be the best marker of hypochlorite-mediated collagen oxidation.

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Oxidative modification of ovalbumin.

Cited by 27 publications

References 24 publications

Alteration of an Autoantigen by Chlorination, a Process Occurring During Inflammation, Can Overcome Adaptive Immune Tolerance

Alteration of an Autoantigen by Chlorination, a Process Occurring During Inflammation, Can Overcome Adaptive Immune Tolerance

Arthritogenicity of collagen type II is increased by chlorination

Collagen type II modification by hypochlorite.

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