Neutrophil-induced lung damage after hepatic ischemia and endotoxemia (original) (raw)
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The Annals of Thoracic Surgery, 2000
lung injury Superoxide possibly produced in endothelial cells mediates the neutrophil-induced http://ats.ctsnetjournals.org/cgi/content/full/69/2/402 on the World Wide Web at: The online version of this article, along with updated information and services, is located Print ISSN: 0003-4975; eISSN: 1552-6259. Southern Thoracic Surgical Association.
Diethylmaleate, a pro-oxidant, attenuates experimental ischaemia-reperfusion-induced lung injury
British Journal of Surgery, 2002
Background:Systemic ischaemia–reperfusion (IR) injury is in part an oxidant injury mediated by neutrophils. Diethylmaleate (DEM), an intracellular pro-oxidant agent, has been shown to alleviate neutrophil-mediated tissue injury. The aim of this study was to evaluate whether DEM could have a protective effect on neutrophil-mediated lung injury in an animal model of lower-torso IR.Systemic ischaemia–reperfusion (IR) injury is in part an oxidant injury mediated by neutrophils. Diethylmaleate (DEM), an intracellular pro-oxidant agent, has been shown to alleviate neutrophil-mediated tissue injury. The aim of this study was to evaluate whether DEM could have a protective effect on neutrophil-mediated lung injury in an animal model of lower-torso IR.Methods:Sprague–Dawley rats (seven per group) were randomized into three groups. The control group underwent midline laparotomy only; the IR group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; and the third group was pretreated with DEM 6 mmol/kg intraperitoneally 1 h before the IR insult.Sprague–Dawley rats (seven per group) were randomized into three groups. The control group underwent midline laparotomy only; the IR group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; and the third group was pretreated with DEM 6 mmol/kg intraperitoneally 1 h before the IR insult.Results:IR resulted in a significant increase in both microvascular leakage and pulmonary neutrophil infiltration as measured by bronchoalveolar lavage protein concentration and pulmonary myeloperoxidase activity respectively. Pretreatment with DEM significantly attenuated both microvascular leakage and neutrophil infiltration.IR resulted in a significant increase in both microvascular leakage and pulmonary neutrophil infiltration as measured by bronchoalveolar lavage protein concentration and pulmonary myeloperoxidase activity respectively. Pretreatment with DEM significantly attenuated both microvascular leakage and neutrophil infiltration.Conclusion:Preconditioning with DEM protected against IR-induced lung injury. This protective effect raises the possibility of using pro-oxidants to prevent inflammatory injury. © 2002 British Journal of Surgery Society LtdPreconditioning with DEM protected against IR-induced lung injury. This protective effect raises the possibility of using pro-oxidants to prevent inflammatory injury. © 2002 British Journal of Surgery Society Ltd
Anesthesia & Analgesia, 2004
Small-dose endotoxin (Etx) prevents pulmonary perfusion redistribution away from edematous dorsal lung regions after oleic acid (OA)-induced injury in dogs, causing a significant deterioration in oxygenation. We hypothesized that small-dose Etx might mediate this effect via polymorphonuclear neutrophil (PMN) priming with release of inflammatory mediators such as platelet activating factor (PAF) or secretory phospholipase A 2 (sPLA 2 ). To test this hypothesis, we administered specific inhibitors directed against each mediator and used two strategies to generate neutropenia. PAF and sPLA 2 inhibitors were administered before OA injury, followed 2 h later by small-dose Etx (n ϭ 4 each
Effects of TNF-Α-Converting Enzyme Inhibition on Acute Lung Injury Induced by Endotoxin in the Rat
Shock, 2009
We studied the effects of TNF-converting enzyme inhibition with Y-41654, which down-regulates the production of soluble TNF-! (sTNF-!), on acute lung injury induced by intratracheal administration of LPS. We first verified in vitro that pretreatment of isolated alveolar macrophages from Sprague-Dawley male rats with 20 2L of 0.1-mM Y-41654, decreased significantly (P G 0.05) the concentration of sTNF-! in cell supernatants induced by 10 2g/mL of LPS. We then studied four groups of rats (each n = 10) including 1) a control group, 2) an LPS group (300 2g /kg, instilled intratracheally), 3) a Y-41654 group, and 4) a treatment group treated with Y-41654 after LPS instillation. Y-41654, 10 mg/kg in 0.7 mL of phosphate-buffered saline, was administered (i.v.), 15 min before and 0.5, 1.5, 2.5, and 3.5 h after saline or LPS instillation. The animals were observed for 4 h. In the animals treated with Y-41654, the concentrations of sTNF-! and protein in bronchoalveolar lavage fluid, and the number of neutrophils in lung tissue and bronchoalveolar lavage fluid were significantly lower at 4 h than in the LPS group (P G 0.05). In conclusion, sTNF-! plays an important role in the development of acute lung injury induced by intratracheal administration of LPS, in part modulating neutrophil kinetics.
Oxidative Stress and Lung Ischemia-Reperfusion Injury
Oxidative Medicine and Cellular Longevity, 2015
Ischemia-reperfusion (IR) injury is directly related to the formation of reactive oxygen species (ROS), endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients.
Journal of Clinical Investigation, 1995
The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. One of the striking consequences of liver injury is the associated pulmonary dysfunction that may be related to the release of hepatic-derived cytokines. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and demonstrated that this injury causes the production and release of hepatic-derived TNF, which mediates a neutrophil-dependent pulmonary microvascular injury. In this study, we have extended these previous observations to assess whether an interrelationship between TNF and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein-78 (ENA-78), exists that may be accountable for the pathology of lung injury found in this model. In the context of hepatic ischemia/reperfusion injury, we demonstrated the following alterations in lung pathophysiology: (a) an increase in pulmonary microvascular permeability, lung neutrophil sequestration, and production of pulmonary-derived ENA-78; (b) passive immunization with neutralizing TNF antiserum resulted in a significant suppression of pulmonary-derived and (c) passive immunization with neutralizing ENA-78 antiserum resulted in a significant attenuation of pulmonary neutrophil sequestration and microvascular permeability similar to our previous studies with anti-TNF. These findings support the notion that pulmonary ENA-78 produced in response to hepatic-derived TNF is an important mediator of lung injury. (J. Clin. Invest. 1995.95:134-141.)
Oxidant-Antioxidant Balance in Acute Lung Injury*
Chest, 2002
Ethanol induces the expression of ␣1(I) procollagen mRNA in a co-culture system containing a liver stellate cell-line and freshly isolated hepatocytes. Biochim Biophys Acta 1997; 1362:135-144 Svegliati-Baroni G, Ridolfi F, Di Sario A, et al. Intracellular signaling pathways involved in acetaldehyde-induced collagen and fibronectin gene expression in human hepatic stellate