Antibodies against Malondialdehyde (MDA) in MRL/lpr/lprMice: Evidence for an Autoimmune Mechanism Involving Lipid Peroxidation

Yahya, M. Danial; Pinnas, Jacob L.; Meinke, Geraldine C.; Lung, Chien‐Cheng

doi:10.1006/jaut.1996.0002

Cited by 22 publications

(18 citation statements)

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“…Furthermore, carbonyl-modified proteins are highly immunogenic and lead to the formation of neoantigens in the form of carbonylated self-protein (24)(25)(26). This in turn leads to the formation of autoimmune-type responses as a result of altered self-antigens (26)(27)(28). Protein carbonylation is a heterogeneous event, and it is unlikely that only one particular carbonyl modification will impart antigenicity to a protein, as demonstrated here by the immunoreactivity toward protein modified by several different carbonylating species.…”

Section: Discussionmentioning

confidence: 99%

“…We have demonstrated that carbonyl adducts, which are potent antigens formed as a result of exposure to chronic oxidative stress (27), such as cigarette smoking or ozone exposure, can trigger an antibody-mediated immune response. Using in vivo models, two groups have shown that oxidant stress and carbonyl-modified protein can lead to autoimmunity (28,31) with specific T cell activation and corresponding antibody production, a prerequisite for any immune response. Similarly, we found that oxidant-stressed mice after chronic ozone exposure exhibited higher antibody titers against carbonyl-modified protein as well as increased activation of their splenocytes in response to stimulation with carbonyl-modified protein.…”

Section: Discussionmentioning

confidence: 99%

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Oxidative Stress–induced Antibodies to Carbonyl-modified Protein Correlate with Severity of Chronic Obstructive Pulmonary Disease

Kirkham

Caramori

Casolari

et al. 2011

Am J Respir Crit Care Med

165

119

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Rationale: There is increasing evidence for the presence of autoantibodies in chronic obstructive pulmonary disease (COPD). Chronic oxidative stress is an essential component in COPD pathogenesis and can lead to increased levels of highly reactive carbonyls in the lung, which could result in the formation of highly immunogenic carbonyl adducts on "self" proteins. Objectives: To determine the presence of autoantibodies to carbonylmodified protein in patients with COPD and in a murine model of chronic ozone exposure. To assess the extent of activated immune responses toward carbonyl-modified proteins. Methods: Blood and peripheral lung were taken from patients with COPD, age-matched smokers, and nonsmokers with normal lung function, as well as patients with severe persistent asthma. Mice were exposed to ambient air or ozone for 6 weeks. Antibody titers were measured by ELISA, activated compliment deposition by immunohistochemistry, and cellular activation by ELISA and fluorescenceactivated cell sorter. Measurements and Main Results: Antibody titer against carbonylmodified self-protein was significantly increased in patients with Global Initiative for Chronic Obstructive Lung Disease stage III COPD compared with control subjects. Antibody levels inversely correlated with disease severity and showed a prevalence toward an IgG1 isotype. Deposition of activated complement in the vessels of COPD lung as well as autoantibodies against endothelial cells were also observed. Ozone-exposed mice similarly exhibited increased antibody titers to carbonyl-modified protein, as well as activated antigen-presenting cells in lung tissue and splenocytes sensitized to activation by carbonylmodified protein.Conclusions: Carbonyl-modified proteins, arising as a result of oxidative stress, promote antibody production, providing a link by which oxidative stress could drive an autoimmune response in COPD.Keywords: COPD; autoimmunity; oxidative stress; carbonyl Chronic obstructive pulmonary disease (COPD) is currently a leading cause of morbidity and mortality worldwide (1), with the main cause being long-term cigarette smoking in the western world (1, 2). Inflammation and remodeling of the small airways are major determinants for the progression and severity of COPD, as defined by the decline in FEV 1 (3). Accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells, such as CD4 1 cells, CD8 1 cells, B cells, macrophages, and neutrophils, and the formation of lymphoid follicles are all features of the observed inflammation that correlate with the severity of COPD (3, 4).Previous studies have suggested that autoimmune mechanisms may contribute to the pathogenesis of COPD. Serum autoantibodies against elastin (5) and bronchial epithelial cells along with corresponding IgG and complement (C3) deposition (6) have been observed in COPD lung. It has therefore been proposed that cigarette smoke-derived antigens may be responsible for driving this disease process in COPD (...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Oxidative Stress–induced Antibodies to Carbonyl-modified Protein Correlate with Severity of Chronic Obstructive Pulmonary Disease

Kirkham

Caramori

Casolari

et al. 2011

Am J Respir Crit Care Med

165

119

View full text Add to dashboard Cite

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“…The observations suggest that gemcitabine could significantly induce the lipid peroxidation process. MDA is a highly reactive three-carbon dialdehyde produced as a byproduct of polyunsaturated fatty acid peroxidation and arachidonic acid metabolism 15 . But the MDA (-13.53 %) content were significantly reduced in comparison to gemcitabine-treated group when tissue homogenates were treated with gemcitabine in combination with morin.…”

Section: Resultsmentioning

confidence: 99%

Estimation of Gemcitabine-Induced Lipid Peroxidation Using Common Laboratory Markers: Role of Morin

Ray¹

2018

Int. Res. J. Pharm.

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The objective of the present in vitro study was to explore antiperoxidative potential of morin on gemcitabine-induced lipid peroxidation. Goat liver tissue homogenate was used as source of lipid. Two common laboratory markers such as malondialdehyde and reduced glutathione were used for the model. The results showed that gemcitabine has the ability to induce lipid peroxidation to a significant extent and it was also found that morin has the ability to suppress the gemcitabine-induced toxicity.

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“…The observations suggest that paclitaxel could significantly induce the lipid peroxidation process. MDA is a highly reactive three-carbon dialdehyde produced as a byproduct of polyunsaturated fatty acid peroxidation and arachidonic acid metabolism 17 . But the MDA (5.28 %) content was significantly reduced in comparison to paclitaxel-treated group when tissue homogenates were treated with paclitaxel in combination with water extract of Spirulina platensis.…”

Section: Resultsmentioning

confidence: 99%

Paclitaxel Induced Lipid Peroxidation: Role of Water Extract of Spirulina Platensis

Ray¹

2016

J. Pharm. Sci. Innov.

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The present study showed the free radical scavenging activity of water extract of Spirulina platensis on paclitaxel-induced lipid peroxidation. This in vitro work was carried out with goat liver as lipid source using malondialdehyde and 4-hydroxy-2-nonenal as model markers. The findings suggest that paclitaxel could induce lipid peroxidation to a significant extent and it was also found that water extract of the Spirulina platensis has the ability to suppress the paclitaxel-induced toxicity.

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Antibodies against Malondialdehyde (MDA) in MRL/lpr/lprMice: Evidence for an Autoimmune Mechanism Involving Lipid Peroxidation

Cited by 22 publications

References 0 publications

Oxidative Stress–induced Antibodies to Carbonyl-modified Protein Correlate with Severity of Chronic Obstructive Pulmonary Disease

Oxidative Stress–induced Antibodies to Carbonyl-modified Protein Correlate with Severity of Chronic Obstructive Pulmonary Disease

Estimation of Gemcitabine-Induced Lipid Peroxidation Using Common Laboratory Markers: Role of Morin

Paclitaxel Induced Lipid Peroxidation: Role of Water Extract of Spirulina Platensis

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