Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Recent evidence suggests that cell therapy such as the injection of bone marrow-derived mononuclear cells (BMMNCs) can exert protective effects in various conditions associated with ischemia-reperfusion injury. Here, we investigate the effects of BMMNCs on the organ injury/dysfunction induced by hemorrhagic shock (HS). Thirty-seven anesthetized male Wistar rats were subjected to hemorrhage by reducing mean arterial pressure to 35 ± 5 mmHg for 90 min, followed by resuscitation with 20 mL/kg Ringer's lactate administered over 10 min and 50% of the shed blood over 50 min. ⋯ Hemorrhagic shock resulted in significant organ injury/dysfunction (renal, hepatic, neuromuscular) and inflammation (hepatic, lung). In rats subjected to HS, administration of BMMNCs significantly attenuated (i) organ injury/dysfunction (renal, hepatic, neuromuscular) and inflammation (hepatic, lung), (ii) increased the phosphorylation of Akt and glycogen synthase kinase-3β, (iii) attenuated the activation of nuclear factor-κB, (iv) attenuated the increase in extracellular signal-regulated kinase 1/2 phosphorylation, and (v) attenuated the increase in expression of intercellular adhesion molecule-1. Our findings suggest that administration of BMMNCs protects against the induction of early organ injury/dysfunction caused by severe HS by a mechanism that may involve activation of Akt and the inhibition of glycogen synthase kinase-3β and nuclear factor-κB.
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Pulmonary contusion is a major cause of respiratory failure in trauma patients. This injury frequently leads to immune suppression and infectious complications such as pneumonia. The mechanism whereby trauma leads to an immune-suppressed state is poorly understood. ⋯ Toll-like receptor 4 expression on alveolar macrophages was significantly elevated in the injured group compared with sham but not in neutrophils. Animals subjected to PC are more resistant to mortality from infection with Pa and display an enhanced cytokine response when subsequently subjected to Pa. Increased expression of toll-like receptor 4 on alveolar macrophages and enhanced innate immunity are a possible mechanism of increased cytokine production and decreased susceptibility to pneumonia.
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Patients with crush injury often present systemic inflammatory response syndrome and fall into multiple organ failure. The mechanism by which the local tissue damage induces distant organ failure is still unclear. We focused on high-mobility group box 1 protein (HMGB1) as one of the damage-associated molecular pattern molecules that cause systemic inflammation in crush injury. ⋯ These results indicate that HMGB1 is released in response to damage immediately after crush injury and acts as a proinflammatory mediator. Administration of anti-HMGB1 antibody reduced inflammatory reactions and improved survival by blocking extracellular HMGB1. Thus, HMGB1 appears to be a therapeutic target, and anti-HMGB1 antibody may become a promising novel therapy against crush injury to prevent the progression to multiple organ failure.
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Gram-negative bacteria remain the leading cause of sepsis, a disease that is consistently in the top 10 causes of death internationally. Curing bacteremia alone does not necessarily end the disease process as other factors may cause inflammatory damage. Bacterial outer membrane vesicles (OMVs) are naturally produced blebs from the outer membrane of gram-negative bacteria, which contain various proteins and lipopolysaccharide (LPS). ⋯ Downstream events such as the recruitment of neutrophils into tissues due to the presentation of vascular adhesion molecules also occur in OMV-treated animals. Although soluble LPS elicits stronger responses than did OMVs, responses to the latter consistently exceeded those associated with lactated Ringer's infusion. These results indicate OMVs, independent of the parent bacteria, do initiate an inflammatory response; however, further studies are required to better characterize the temporal biomolecular interactions involved.