Enhanced Lung Injury and Delayed Clearance of<i>Pneumocystis carinii</i>in Surfactant Protein A-Deficient Mice: Attenuation of Cytokine Responses and Reactive Oxygen-Nitrogen Species

Atochina, Elena N.; Beck, James M.; Preston, Angela M.; Haczku, Angela Franciska; Tomer, Yaniv; Scanlon, Seth Thomas; Fusaro, Trevor; Casey, John; Hawgood, Samuel; Gow, Andrew J.; Beers, Michael F.

doi:10.1128/iai.72.10.6002-6011.2004

Cited by 62 publications

(50 citation statements)

References 70 publications

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“…It is becoming clear from animal models and human studies that the complex oligomeric structure of SP-D and its liability for disruption in disease models call for a comprehensive analysis of SP-D (36). The availability of new antisera (39) with better specificity for murine and human SP-D than we used previously, and the advent of new techniques including the biotin-switch assay to detect S-nitrosyl protein modifications and native gel electrophoresis to examine the quaternary structure of SP-D, enabled us to revisit the role of SP-D in HPS. In the current study, we found both increases in total SP-D and SNO-SP-D in HPS BAL from both EPPE mice and patients with HPS1.…”

Section: Discussionmentioning

confidence: 99%

Early Alveolar Epithelial Dysfunction Promotes Lung Inflammation in a Mouse Model of Hermansky-Pudlak Syndrome

Atochina‐Vasserman

Bates

Zhang

et al. 2011

Am J Respir Crit Care Med

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Rationale: The pulmonary phenotype of Hermansky-Pudlak syndrome (HPS) in adults includes foamy alveolar type 2 cells, inflammation, and lung remodeling, but there is no information about ontogeny or early disease mediators. Objectives: To establish the ontogeny of HPS lung disease in an animal model, examine disease mediators, and relate them to patients with HPS1. Methods: Mice with mutations in both HPS1/pale ear and HPS2/ AP3B1/pearl (EPPE mice) were studied longitudinally. Total lung homogenate, lung tissue sections, and bronchoalveolar lavage (BAL) were examined for phospholipid, collagen, histology, cell counts, chemokines, surfactant protein D (SP-D), and S-nitrosylated SP-D. Isolated alveolar epithelial cells were examined for expression of inflammatory mediators, and chemotaxis assays were used to assess their importance. Pulmonary function test results and BAL from patients with HPS1 and normal volunteers were examined for clinical correlation. Measurements and Main Results: EPPE mice develop increased total lung phospholipid, followed by a macrophage-predominant pulmonary inflammation, and lung remodeling including fibrosis.

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Section: Discussionmentioning

confidence: 99%

Early Alveolar Epithelial Dysfunction Promotes Lung Inflammation in a Mouse Model of Hermansky-Pudlak Syndrome

Atochina‐Vasserman

Bates

Zhang

et al. 2011

Am J Respir Crit Care Med

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“…5 Compelling evidence was provided to support the importance of SP-A and SP-D in innate immune function by studies on gene-deficient mice. Animals lacking either lung collectins have shown an increased susceptibility to bacterial, 6-8 viral, [9][10][11] fungal, 12 endotoxin, 13 and allergen-induced 14,15 lung inflammation. Under normal conditions, however, SP-A −/− mice display no pathologic features in the lung.…”

Section: Tnf; Sp-d; Dendritic Cell; Mouse Model; Airway Inflammationmentioning

confidence: 99%

Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice

Hortobagyi

Kierstein

Krytska

et al. 2008

Journal of Allergy and Clinical Immunology

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“…8). (3,6,45,46) as well as to noninfectious bleomycin-induced lung injury (17) has been previously reported. Protection of surfactant phospholipids and macrophages from oxidative damage in vitro by direct antioxidant functions of SP-D has also been observed (16).…”

Section: Sp-dmentioning

confidence: 99%

SP-D-deficient mice are resistant to hyperoxia

Jain¹,

Atochina‐Vasserman²,

Kadire³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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surfactant protein D; inflammation; alveolar macrophages; collectin AS A BYPRODUCT OF THE USE of high oxygen (O 2 ) concentrations often required in management of patients with respiratory failure, reactive oxygen species produced during hyperoxic exposure can adversely affect the lung. It has been proposed that the balance between oxygen radical production and antioxidant capacities can modulate oxygen-mediated injury. The lung responds to hyperoxia by enhancing the expression of cytoprotective proteins including antioxidants (65), DNA repair enzymes (55), and regulators of cell survival. In addition, elevated expression of certain surfactant components occurs in lungs of adult (54) and neonatal rats (64) during adaptation to both sublethal (85%) and lethal (95%) oxygen (1).Surfactant protein D (SP-D), an airway epithelial secretory product, belongs to the superfamily of mammalian C-type (Ca 2ϩ -binding) lectins (collectins), which also includes SP-A and serum mannose-binding lectin. Like all collectins, monomeric SP-D is distinguished by the presence of an NH 2 -terminal cysteine-rich domain, a collagen domain, a coiled-coil neck domain, and a lectin domain with calcium-dependent regulatory elements. SP-D monomers associate through their collagenous domains to form a basic functional trimer, which then associates into higher order multimers. This oligomeric assembly provides high avidity, affinity, and specificity to SP-D ligand recognition. In the lung, SP-D ligands include allergens, particles, bacterial cell wall components, and viral envelope proteins (26). SP-D is also known to be chemotactic for neutrophils and mononuclear phagocytes (25) and to modulate alveolar type II (61) and macrophage function in vitro (39).SP-D is produced primarily by alveolar type II cells and nonciliated bronchiolar cells in the lung (24) and is constitutively secreted into the alveoli where it influences surfactant homeostasis (40), effector cell functions, and host defense. It is upregulated in a variety of inflammatory and infectious conditions including Pneumocystis pneumonia (5), asthma (2), and bleomycin injury (17). Mice or rats exposed to hyperoxic challenge also have increases in SP-D (13), suggesting that it may have a role in protection from this insult.Targeted disruption of the SP-D gene in vivo in two genetically different backgrounds has been shown to result in mice with increased alveolar and cellular pools of surfactant phospholipid, accelerated development of age-related emphysema, and large, foamy macrophages (14,40). These SP-D null mice (SP-D Ϫ/Ϫ ) also exhibit an increase in the baseline level of inflammation in the lung, increases in metalloproteinase activity, and biochemical evidence of enhanced oxidative-nitrative stress (4, 63). In addition, SP-D deficiency also confers susceptibility to specific bacterial (45) and viral infections (46).We have previously reported modulation of bleomycininduced lung injury by SP-D. In SP-D Ϫ/Ϫ mice, we showed increased susceptibility to bleomycin and evidence of oxida...

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Enhanced Lung Injury and Delayed Clearance ofPneumocystis cariniiin Surfactant Protein A-Deficient Mice: Attenuation of Cytokine Responses and Reactive Oxygen-Nitrogen Species

Cited by 62 publications

References 70 publications

Early Alveolar Epithelial Dysfunction Promotes Lung Inflammation in a Mouse Model of Hermansky-Pudlak Syndrome

Early Alveolar Epithelial Dysfunction Promotes Lung Inflammation in a Mouse Model of Hermansky-Pudlak Syndrome

Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice

SP-D-deficient mice are resistant to hyperoxia

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