Alveolar Surfactant Protein D Content Modulates Bleomycin-induced Lung Injury

Casey, John; Kaplan, Jennifer; Atochina‐Vasserman, Elena N.; Gow, Andrew J.; Kadire, Helchem; Tomer, Yaniv; Fisher, James H.; Hawgood, Samuel; Savani, Rashmin C.; Beers, Michael F.

doi:10.1164/rccm.200505-767oc

Cited by 48 publications

(64 citation statements)

References 57 publications

(76 reference statements)

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“…In SP-D Ϫ/Ϫ mice, we showed increased susceptibility to bleomycin and evidence of oxidative-nitrative stress (17). Similar findings were observed when the same mice were infected with Pneumocystis carinii (6).…”

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confidence: 84%

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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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supporting

confidence: 84%

“…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.…”

mentioning

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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“…We have previously shown that SP-D null mice demonstrate enhanced susceptibility to intratracheal administration of bleomycin, whereas SP-D overexpressing mice were protected (14). Based on these results and on data showing increased oxidative stress in SP-D null mice, we hypothesized a protective role for SP-D in hyperoxic lung injury.…”

mentioning

confidence: 86%

“…Mice overexpressing the rat isoform of SP-D (rSP-D) in a lung-specific fashion using the human 23.7 kb SP-C promoter on the Swiss Black (SWB) background (SP-D OE) were provided by Dr. Frank McCormack and have been described previously (14,20). Heterozygous transgenic mice carrying a single concatamer of the rSP-D transgene were crossed with wild-type SWB mice to generate SP-D OE mice and littermate control (wild-type [WT]) mice.…”

Section: Sp-d Oe Micementioning

confidence: 99%

“…In vivo, the use of transgenic mouse models suggests a protective role for SP-D against damage by inflammatory stimuli. Local up-regulation of SP-D protein levels in wild-type mice occurs after a variety of infectious and inflammatory lung injuries, including bacterial and fungal pneumonia, bleomycin, and hyperoxia (12)(13)(14), while mice constitutively deficient in SP-D develop, at baseline, progressive lung inflammation and time-dependent airspace remodeling (15).…”

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Surfactant Protein D Protects against Acute Hyperoxic Lung Injury

Jain

Atochina‐Vasserman

Tomer

et al. 2008

Am J Respir Crit Care Med

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, SP-D OE mice exposed to 80% O 2 demonstrated substantially increased survival accompanied by significant reductions in wet to dry lung ratios and bronchoalveolar lavage (BAL) protein. Although SP-D OE and WT mice exhibited a twofold increase in total BAL cells and neutrophilia in response to hyperoxia, the SP-D OE group had lower levels of BAL proinflammatory cytokines and chemokines, including IL-6, tumor necrosis factor-a, and monocyte chemotactic protein-1; increased mRNA levels of the transcription factor NF-E2 related factor-2 (NRF-2) and phase 2 antioxidants hemoxygenase-1 (HO-1), glutathione peroxidase-2 (GPx-2) and NAD(P)H quinone oxidoreductase-1 (Nqo-1); and decreases in lung tissue thiobarbituric acid-reactive substances. As proof of principle, the protective role of SP-D on hyperoxic injury was confirmed as SP-D Dox-on mice exposed to 85% O 2 demonstrated increased mortality upon withdrawal of doxycycline. Conclusions: Local expression of SP-D protects against hyperoxic lung injury through modulation of proinflammatory cytokines and antioxidant enzymatic scavenger systems.

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Danger‐associated molecular patterns (DAMPs) in acute lung injury

Tolle

Standiford

2012

The Journal of Pathology

133

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Danger-associated molecular patterns (DAMPs) are host-derived molecules that can function to regulate the activation of pathogen recognition receptors (PRRs). These molecules play a critical role in modulating the lung injury response. DAMPs originate from multiple sources, including injured and dying cells, the extracellular matrix, or exist as immunomodulatory proteins within the airspace and interstitium. DAMPs can function as either toll-like receptor (TLR) agonists or antagonists, and can modulate both TLR and nod-like receptor (NLR) signalling cascades. Collectively, this diverse group of molecules may represent important therapeutic targets in the prevention and/or treatment of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS).

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Alveolar Surfactant Protein D Content Modulates Bleomycin-induced Lung Injury

Abstract: These data provide new in vivo evidence for an antiinflammatory role for SP-D in response to noninfectious, subacute lung injury via modulation of oxidative-nitrative stress.

Cited by 48 publications

References 57 publications

SP-D-deficient mice are resistant to hyperoxia

SP-D-deficient mice are resistant to hyperoxia

Surfactant Protein D Protects against Acute Hyperoxic Lung Injury

Danger‐associated molecular patterns (DAMPs) in acute lung injury

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