Danger‐associated molecular patterns (<scp>DAMPs</scp>) in acute lung injury

Tolle, Leslie; Standiford, Theodore J.

doi:10.1002/path.4124

Cited by 133 publications

(101 citation statements)

References 135 publications

(147 reference statements)

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“…We previously reported that elevated IL-10 and reduced IL-12p70 in bronchial washings were statistically significantly associated with ALI following inhalation injury (14). It has been postulated that DAMPs released from damaged tissues drive immune dysfunction after injury (3,16,27). We therefore hypothesized that increased DAMPs released from damaged tissue would correlate with bacterial infection and IL-10/IL-12p70 levels.…”

Section: Discussionmentioning

confidence: 92%

“…The primary function of TLR is to be "pattern recognition receptors" for the innate immune system, capable of sensing molecules normally associated with microorganisms (1,2). Endogenous ligands also exist for mammalian innate receptors with both necrotic and apoptotic cells able to induce cell signaling through TLR and other innate sensing molecules via release of endogenous ligands, known as DAMPS such as HA, ds-DNA, HSP-70, and HMGB-1 (3,27). We and others have shown that TLR expression and signaling is often altered after injury leading to hypo-or hyper-responsiveness (10,18).…”

Section: Discussionmentioning

confidence: 99%

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Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury

Maile

Jones

Pan

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Bacterial infection is a major cause of morbidity affecting outcome following burn and inhalation injury. While experimental burn and inhalation injury animal models have suggested that mediators of cell damage and inflammation increase the risk of infection, few studies have been done on humans. This is a prospective, observational study of patients admitted to the North Carolina Jaycee Burn Center at the University of North Carolina who were intubated and on mechanical ventilation for treatment of burn and inhalational injury. Subjects were enrolled over a 2-yr period and followed till discharge or death. Serial bronchial washings from clinically indicated bronchoscopies were collected and analyzed for markers of tissue injury and inflammation. These include damage-associated molecular patterns (DAMPs) such as hyaluronic acid (HA), double-stranded DNA (dsDNA), heat-shock protein 70 (HSP-70), and high-mobility group protein B-1 (HMGB-1). The study population was comprised of 72 patients who had bacterial cultures obtained for clinical indications. Elevated HA, dsDNA, and IL-10 levels in bronchial washings obtained early (the first 72 h after injury) were significantly associated with positive bacterial respiratory cultures obtained during the first 14 days postinjury. Independent of initial inhalation injury severity and extent of surface burn, elevated levels of HA dsDNA and IL-10 in the central airways obtained early after injury are associated with subsequent positive bacterial respiratory cultures in patients intubated after acute burn/inhalation injury.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury

Maile

Jones

Pan

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Several triggering conditions, including hemorrhagic shock, endotoxin, trauma, burn injury, and ischemia–reperfusion, contribute to ALI and exaggerate the inflammatory process of ALI [23–25]. NF-κB is an important nuclear transcription factor that upon activation, transfers into the nucleus, amplifying inflammatory responses by promoting production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8 [26, 27].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine ameliorates acute lung injury following orthotopic autologous liver transplantation in rats probably by inhibiting Toll-like receptor 4–nuclear factor kappa B signaling

Chi¹,

Wei²,

Gao³

et al. 2015

J Transl Med

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BackgroundTo investigate whether pretreatment with dexmedetomidine (Dex) has a protective effect against acute lung injury (ALI) in an orthotopic autologous liver transplantation (OALT) rat model and to explore the mechanisms responsible for the protective effect of Dex against lung injury.MethodsForty-eight rats underwent OALT and were randomly divided into six groups (n = 8 in each group) that received 10 µg/kg Dex, 50 µg/kg Dex, 50 µg/kg Dex + nonspecific α2-adrenergic receptor (AR) antagonist atipamezole, 50 µg/kg Dex + specific α2B/C-AR antagonist ARC-239, 50 µg/kg Dex + specific α2A-AR antagonist BRL-44408, or the same amount of normal saline. The sham rats (n = 8) underwent anesthesia induction, laparotomy, and separation of the portal vein without liver ischemia and reperfusion. Lung tissue sections were stained with hematoxylin and eosin (HE) to visualize the damage. The expression of Toll-like receptor 4 (TLR4) and the phospho-nuclear factor (NF)-κB p65 subunit as well as inflammatory cytokines was measured.ResultsRats exhibited increased histological lung injury scores and pulmonary edema following OALT. Pretreatment with 50 μg/kg Dex attenuated OALT-induced lung injury in rats, probably by inhibiting the activation of the TLR4–NF-κB signaling pathway. The protective effect of Dex could be blocked by atipamezole or BRL-44408, but not by ARC-239, suggesting these effects of Dex were mediated, at least in part, by the α2A-AR.ConclusionsDex exerts protective effects against ALI following OALT, and this protection is associated with the suppression of TLR4–NF-κB signaling. Thus, pretreatment with Dex may be a useful method for reducing lung damage caused by liver transplantation.

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“…In our aspiration model, increased expression of RAGE in the lung, upregulated by high dietary AGEs, constitutes the ‘first hit’. The ‘second hit’ comes from the low-pH cellular injury of gastric aspiration, releasing a variety of endogenous danger signals known as damage associated molecular patterns (DAMPs) [11]. …”

Section: Introductionmentioning

confidence: 99%

Dietary advanced glycation end-products, its pulmonary receptor, and high mobility group box 1 in aspiration lung injury

Smit

Guo

Davidson

et al. 2014

Journal of Surgical Research

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Background Gastric aspiration is a significant cause of acute lung injury and acute respiratory distress syndrome. Environmental risk factors, such as a diet high in pro-inflammatory advanced glycation end-products (AGEs), may render some patients more susceptible to lung injury after aspiration. We hypothesized that high dietary AGEs increase its pulmonary receptor, RAGE, producing an amplified pulmonary inflammatory response in the presence of high mobility group box 1 (HMGB1), a RAGE ligand and an endogenous signal of epithelial cell injury after aspiration. Materials and Methods CD-1 mice were fed either a low AGE (LAGE) or high AGE (HAGE) diet for 4 weeks. After aspiration injury with acidified small gastric particles, bronchial alveolar lavage (BAL) and whole-lung tissue samples were collected at 5 minutes, 1 hour, 5 hours, and 24 hours post-injury. RAGE, soluble RAGE (sRAGE), HMGB1, cytokine and chemokine concentrations, albumin levels, neutrophil influx, and lung myeloperoxidase (MPO) activity were measured. Results We observed that HAGE-fed mice exhibited greater pulmonary RAGE levels before aspiration and increased BAL sRAGE levels after aspiration compared to LAGE-fed mice. Lavage HMGB1 levels rose immediately after aspiration, peaking at 1 hour, and strongly correlated with sRAGE levels in both dietary groups. HAGE-fed mice demonstrated higher cytokine and chemokine levels with increased pulmonary MPO activity over 24 hours versus LAGE-fed mice. Conclusions This study indicates that high dietary AGEs can increase pulmonary RAGE, augmenting the inflammatory response to aspiration in the presence of endogenous damage signals such as HMGB1.

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

Cited by 133 publications

References 135 publications

Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury

Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury

Dexmedetomidine ameliorates acute lung injury following orthotopic autologous liver transplantation in rats probably by inhibiting Toll-like receptor 4–nuclear factor kappa B signaling

Dietary advanced glycation end-products, its pulmonary receptor, and high mobility group box 1 in aspiration lung injury

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