Surfactant lipid peroxidation damages surfactant protein A and inhibits interactions with phospholipid vesicles

Kuzmenko, Alexander I.; Wu, Huixing; Bridges, James P.; McCormack, Francis X.

doi:10.1194/jlr.m300360-jlr200

Cited by 30 publications

(35 citation statements)

References 53 publications

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“…Several lines of evidence suggest that oxidative damage to surfactant components have critical effects on surfactant biophysical function, but less is known about the consequences of oxidative stress for collectin-mediated host defense (4,18).…”

Section: Discussionmentioning

confidence: 99%

“…The purified proteins were dialyzed for 2 days against daily changes of 2,000 volumes of 5 mM Tris (pH 7.4), 150 mM NaCl and for 1 day against 2,000 volumes of 5 mM Tris (pH 7.4), and stored at Ϫ20°C. The EDTA content of all protein samples used was measured by the method of Kratochvil, with modifications as previously reported (4). The average final EDTA concentration was 5 M, and was less than 25 M in all SP-A reagents used.…”

Section: Methodsmentioning

confidence: 99%

“…Supplemental oxygen therapy is extensively used in this setting, resulting in conditions that favor formation of reactive oxygen species (ROS) 1 and damage to airway cells and extracellular molecules in the alveolar lining fluid. We recently reported that SP-A is oxidatively modified and functionally inactivated, with respect to interaction with phospholipids, upon exposure of SP-A to lipid peroxidation, in vitro (4). We postulate that oxidative damage of SP-A may also affect the host defense activities of the protein.…”

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confidence: 99%

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Surfactant Protein A Is a Principal and Oxidation-sensitive MicrobialPermeabilizing Factor in the Alveolar LiningFluid

Kuzmenko

Wan

et al. 2005

Journal of Biological Chemistry

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We have reported that surfactant protein A kills some Gram-negative organisms by increasing membrane permeability. In this study, we investigated the physiologic importance of this activity and the effect of oxidative stress on the antimicrobial functions of SP-A in vitro and in vivo. Concentrated bronchoalveolar lavage fluids from SP-A؉/؉ mice increased the permeability of the Escherichia coli K12 cell membrane to a greater extent than lavage from SP-A؊/؊ animals. Similarly, calciumdependent surfactant-binding proteins of SP-A؉/؉ mice increased membrane permeability more than those from SP-A؊/؊ mice and produced greater zonal killing of agar-embedded bacteria in a radial diffusion assay. Exposure of human SP-A to copper-initiated surfactant phospholipid peroxidation or to free radicals generated by human neutrophils in vitro increased the level of SP-A-associated carbonyl moieties and blocked the permeabilizing function of the protein. We also found that exposure of mice to 90% O 2 for 4 days, sufficient to lead to consumption of glutathione, oxidation of protein thiols, and accumulation of airspace protein-associated carbonyl moieties, blocked the permeabilizing activity of lavage fluid from SP-A؉/؉ mice. We conclude that SP-A is a major microbial permeablizing factor in lavage fluid and that oxidative stress inhibits the antibacterial activity of SP-A by a mechanism that includes oxidative modification and functional inactivation of the protein.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Surfactant Protein A Is a Principal and Oxidation-sensitive MicrobialPermeabilizing Factor in the Alveolar LiningFluid

Kuzmenko

Wan

et al. 2005

Journal of Biological Chemistry

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“…Oxidized surfactant displays inferior anti-inflammatory and surface tension lowering properties [66,67]. Reactive oxygen species alter the structure of surfactant lipids and proteins inactivating biophysical and immunological properties of surfactant components [68][69][70][71][72][73][74][75][76]. The macrophage scavenger receptors SR-A and MARCO clear oxidized surfactant lipids as a source of inflammation in the alveolus [77].…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Surfactant: An Immunological Perspective

Chroneos

Sever-Chroneos

Shepherd

2010

Cell Physiol Biochem

166

115

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“…Ozone gas also plays a role in generating oxidatively truncated PLs (Uhlson et al 2002). Under normal healthy conditions surfactant is protected from oxidation by maintaining low contents of PUFAs, antioxidant action of glutathione present in the lining fluid and surfactant proteins A and D (Kuzmenko et al 2004). However, the accumulation of biologically active OxPLs products occurs in pathological states due to the oxidation of surfactant PCs, membrane lipids and apoptosis of bronchial cells.…”

Section: Lung Injurymentioning

confidence: 99%