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

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 proinflammatory 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.

Low pH environmental stress inhibits LPS and LTA-stimulated proinflammatory cytokine production in rat alveolar macrophages.

Gastric aspiration increases the risks for developing secondary bacterial pneumonia. Cytokine elaboration through pathogen recognition receptors (PRRs) is an important mechanism in initiating innate immune host response. Effects of low pH stress, a critical component of aspiration pathogenesis, on the PRR pathways were examined, specifically toll-like receptor-2 (TLR2) and TLR4, using isolated rat alveolar macrophages (aMØs).

Role of pulmonary artery reactivity and nitric oxide in injury and inflammation following lung contusion.

The mechanisms contributing to hypoxia in lung contusion (LC) remain unclear and not temporally associated with the peak onset of acute inflammation. We investigated the role of oxidative stress in alteration of pulmonary arterial (PA) reactivity following LC. In addition, the role of antioxidants in reversing this process was examined.

Increasing TNF levels solely in the rat hippocampus produces persistent pain-like symptoms.

The manifestation of chronic, neuropathic pain includes elevated levels of the cytokine tumor necrosis factor-alpha (TNF). Previously, we have shown that the hippocampus, an area of the brain most notable for its role in learning and memory formation, plays a fundamental role in pain sensation. Using an animal model of peripheral neuropathic pain, we have demonstrated that intracerebroventricular infusion of a TNF antibody adjacent to the hippocampus completely alleviated pain.

Role of macrophage chemoattractant protein-1 in acute inflammation after lung contusion.

Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2(-/-)) mice.

Doxorubicin-conjugated quantum dots to target alveolar macrophages and inflammation.

Unlabelled: The ability to provide targeted therapeutic delivery in the lung would be a major advancement in pharmacological treatments for many pulmonary diseases. Critical issues for such successful delivery would require the ability to target specific cell types, minimize toxicity (e.g.

Predictive modeling and inflammatory biomarkers in rats with lung contusion and gastric aspiration.

Background: This study uses statistical predictive modeling and hierarchical cluster analyses to examine inflammatory mediators and cells in bronchoalveolar lavage (BAL) as putative biomarkers in rats with blunt trauma lung contusion (LC), gastric aspiration (combined acid and small gastric food particles, CASP), or a combination of the two.

Methods: Specific parameters assessed in the innate pulmonary inflammatory response were leukocytes, macrophages, and polymorphonuclear neutrophils (PMNs) in BAL; whole lung myeloperoxidase activity; and a series of cytokines or chemokines present in BAL at 5 or 24 hours after injury: tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, interferon-gamma, IL-10, macrophage inflammatory protein-2, cytokine-induced neutrophil chemoattractant-1, and monocyte chemoattractant protein-1.

Results: Rats with LC, CASP, LC + CASP all had severe lung injury compared with uninjured controls based on decreased arterial oxygenation or increased BAL albumin at 5 or 24 hours postinsult.

Superimposed gastric aspiration increases the severity of inflammation and permeability injury in a rat model of lung contusion.

Introduction: Lung contusion (LC) from blunt thoracic trauma is a clinically-prevalent condition that can progress to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Patients with LC are at risk for gastric aspiration at the time of trauma, but the combined insults have not been well-studied in animal models. This study tests the hypothesis that concurrent gastric aspiration (combined acid and small gastric particles, CASP) at the time of trauma significantly increases permeability injury and inflammation compared with LC alone, and also modifies the inflammatory response to include distinct features compared with the aspiration component of injury.

Lung contusion: inflammatory mechanisms and interaction with other injuries.

This article reviews current animal models and laboratory studies investigating the pathophysiology of lung contusion (LC), a common and severe condition in patients with blunt thoracic trauma. Emphasis is on studies elucidating cells, mediators, receptors, and processes important in the innate pulmonary inflammatory response that contribute to LC injury. Surfactant dysfunction in the pathogenesis of LC is also discussed, as is the potential role of epithelial cell or neutrophil apoptosis.

Surfactant dysfunction in lung contusion with and without superimposed gastric aspiration in a rat model.

This study investigates surfactant dysfunction in rats with lung contusion (LC) induced by blunt chest trauma. Rats at 24 h postcontusion had a decreased percent content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL) and altered large-aggregate composition with decreased phosphatidylcholine (PC), increased lyso-PC, and increased protein compared with uninjured controls. The surface activity of large aggregates on a pulsating bubble surfactometer was also severely impaired at 24 h postcontusion.

A rat model for isolated bilateral lung contusion from blunt chest trauma.

Lung contusion affects 17%-25% of adult blunt trauma patients, and is the leading cause of death from blunt thoracic injury. A small animal model for isolated bilateral lung contusion has not been developed. We induced lung contusion in anesthetized rats by dropping a 0.

The evolution of isolated bilateral lung contusion from blunt chest trauma in rats: cellular and cytokine responses.

Lung contusion is the leading cause of death from blunt thoracic trauma in adults, but its mechanistic pathophysiology remains unclear. This study uses a recently developed rat model to investigate the evolution of inflammation and injury in isolated lung contusion. Bilateral lung contusion with minimal cardiac trauma was induced in 54 anesthetized rats by dropping a 0.

Progressive, severe lung injury secondary to the interaction of insults in gastric aspiration.

This study examines lung injury and inflammation over 24 hours following intratracheal instillation of hydrochloric acid (acid), small nonacidic gastric particles (SNAP), or combined acid and small particles (CASP) in adult rats. The severity and duration of injury was significantly greater for CASP compared to acid or SNAP based on PaO2/FiO2, bronchoalveolar lavage (BAL) albumin, and BAL cell numbers. The inflammatory response associated with aspiration injury from CASP was distinct in several respects.

Gastric acid and particulate aspiration injury inhibits pulmonary bacterial clearance.

Objective: To establish a model of secondary bacterial pneumonia following gastric aspiration and to identify possible mechanisms involved in the suppressed antibacterial defenses following the initial pulmonary insult.

Design: A controlled, in vivo laboratory study.

Setting: Research laboratory of a health sciences university.

The effects of Escherichia coli capsule, O-antigen, host neutrophils, and complement in a rat model of Gram-negative pneumonia.

Gram-negative enteric bacilli are agents of life-threatening pneumonia. The role of the bacterial capsule and O-antigen moiety of lipopolysaccharide in the pathogenesis of Gram-negative pneumonia was assessed. In a rat model of pneumonia the LD(50) of a wild-type extraintestinal pathogenic Escherichia coli strain (CP9) was significantly less than its isogenic derivatives deficient in capsule (CP9.

Total extracellular surfactant is increased but abnormal in a rat model of gram-negative bacterial pneumonia.

An in vivo rat model was used to evaluate the effects of Escherichia coli pneumonia on lung function and surfactant in bronchoalveolar lavage (BAL). Total extracellular surfactant was increased in infected rats compared with controls. BAL phospholipid content in infected rats correlated with the severity of alveolar-capillary leak as reflected in lavage protein levels (R(2) = 0.