Evidence for Antibody-Catalyzed Ozone Formation in Bacterial Killing and Inflammation

Wentworth, Paul; McDunn, Jonathan E.; Wentworth, Anita D.; Takeuchi, Cindy; Nieva, Jorgé; Jones, Teresa L.Z.; Bautista, Cristina; Ruedi, J M; Gutierrez, Abel; Janda, Kim D.; Babior, Bernard M.; Eschenmoser, Albert; Lerner, Richard A.

doi:10.1126/science.1077642

Cited by 323 publications

(261 citation statements)

References 19 publications

Supporting

Mentioning

247

Contrasting

Unclassified

Order By: Relevance

“…The range of catalytic efficiency of the autoantibodies was lower than in the case of sequence-specific proteases; e.g., the catalytic efficiency of bovine enterokinase was 7.1⅐10 5 M Ϫ1 ⅐sec Ϫ1 for its natural protein substrate trypsinogen (19). However, the calculated velocities of catalysis by the MBP autoantibodies are among the highest values reported for the antibody catalysis (16,(20)(21)(22)(23) and, therefore, sufficient for their pathological effects during the slow development of neurodegeneration in the course of MS progression.…”

Section: Anti-mbp Antibodies In the Serum Of Ms Patients And Eae Micementioning

confidence: 85%

“…Since the original discovery of catalytic antibodies (30)(31)(32), ample data established their contribution to pathological effects in disease (33) as well as their possible biomedical applications (23,34). It was shown that elevated levels of the autoantibody catalytic activity correlated with an autoimmune response in human and mice models (16,21,35).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen

Пономаренко

Durova

Vorobiev

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

173

231

View full text Add to dashboard Cite

Autoantibody-mediated tissue destruction is among the main features of organ-specific autoimmunity. This report describes ''an antibody enzyme'' (abzyme) contribution to the site-specific degradation of a neural antigen. We detected proteolytic activity toward myelin basic protein (MBP) in the fraction of antibodies purified from the sera of humans with multiple sclerosis (MS) and mice with induced experimental allergic encephalomyelitis. Chromatography and zymography data demonstrated that the proteolytic activity of this preparation was exclusively associated with the antibodies. No activity was found in the IgG fraction of healthy donors. The human and murine abzymes efficiently cleaved MBP but not other protein substrates tested. The sites of MBP cleavage determined by mass spectrometry were localized within immunodominant regions of MBP. The abzymes could also cleave recombinant substrates containing encephalytogenic MBP 85-101 peptide. An established MS therapeutic Copaxone appeared to be a specific abzyme inhibitor. Thus, the discovered epitope-specific antibodymediated degradation of MBP suggests a mechanistic explanation of the slow development of neurodegeneration associated with MS.

show abstract

Section: Anti-mbp Antibodies In the Serum Of Ms Patients And Eae Micementioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen

Пономаренко

Durova

Vorobiev

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

173

231

View full text Add to dashboard Cite

show abstract

“…Another important expected mechanism is antibody-catalyzed ozone formation on the surface of neutrophil PMN cells [59,87], leading to effective killing of bacteria (regardless of the source or antigen specificity of the antibody [87]). …”

Section: The Possible Defense Functions Of Salivary Hsp70 In Mucosal mentioning

confidence: 99%

Potential immunological functions of salivary Hsp70 in mucosal and periodontal defense mechanisms

Fábían

Fejérdy

Nguyen

et al. 2007

Arch. Immunol. Ther. Exp.

View full text Add to dashboard Cite

Molecular chaperones were considered to be intracellular, but there is increasing evidence demonstrating their cytoprotective and immune modulator properties outside the cell. The major extracellular chaperone (Hsp70) was also found in saliva, indicating a possible effect of Hsp70 on mucosal surfaces. Here we summarize the immune-modulatory role of the 70-kDa stress protein family, with special attention on the potential impact of salivary Hsp70 on oral defense mechanisms. There are three major facets of Hsp70-induced immune activation: 1) the appearance of Hsp70 on the surface of certain tumor cells or virally infected cells, leading to their phagocytosis and subsequent lysis; 2) the role of extracellular uncomplexed Hsp70 as a danger signal, leading to the secretion of proinflammatory cytokines from antigen-presenting cells and T lymphocytes and of nitric oxide from macrophages as well as to complement activation; 3) receptor-mediated uptake of peptide-loaded Hsp70 to antigen-presenting cells and cross-presentation of the Hsp70-peptide complex as an antigen to cytotoxic T cells and natural killer lymphocytes. The immune-activating effect of salivary Hsp70 may also be highly important in oral defense, especially in areas where molecular and cellular participants of the immune response appear on the surface of the oral cavity (i.e. several lesions of the mucosa and the periodontal tissues).

show abstract

“…It is not known if some of these occur naturally, and there is a need for methods to make comprehensive studies of the nature and levels of oxysterols in tissues and body fluids. This is illustrated by the recent identification of novel oxysterols, formed from cholesterol by the action of ozone, in human tissues [27][28][29][30]. Evidence has been presented for their involvement in the mediation of inflammatory processes associated with the development of atherosclerotic lesions [28], and in the initiation of protein misfolding as occurs in several neurological diseases [29].…”

mentioning

confidence: 99%

Analysis of oxysterols by electrospray tandem mass spectrometry

Griffiths

Wang

Alvélius

et al. 2006

J. Am. Soc. Mass Spectrom.

103

102

View full text Add to dashboard Cite

Oxysterols are oxygenated derivatives of cholesterol. They are intermediates in cholesterol excretion pathways and may also be regarded as transport forms of cholesterol. The introduction of additional hydroxyl groups to the cholesterol skeleton facilitates the flux of oxysterols across the blood brain barrier, and oxysterols have been implicated in mediating a number of cholesterol-induced metabolic effects. Oxysterols are difficult to analyze by atmospheric pressure ionization mass spectrometry on account of the absence of basic or acidic functional groups in their structures. In this communication, we report a method for the derivatization and analysis of oxysterols by electrospray mass spectrometry. Oxysterols with a 3␤-hydroxy-⌬ 5 structure were converted by cholesterol oxidase to 3-oxo-⌬ 4 steroids and then derivatized with the Girard P reagent to give Girard P hydrazones, which were subsequently analyzed by tandem mass spectrometry. The improvement in sensitivity for the analysis of 25-hydroxycholesterol upon oxidation and derivatization was over 1000. (J Am Soc Mass Spectrom 2006, 17, 341-362)

show abstract

Evidence for Antibody-Catalyzed Ozone Formation in Bacterial Killing and Inflammation

Cited by 323 publications

References 19 publications

Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen

Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen

Potential immunological functions of salivary Hsp70 in mucosal and periodontal defense mechanisms

Analysis of oxysterols by electrospray tandem mass spectrometry

Contact Info

Product

Resources

About