AbstractBackgroundBurn survivors develop long-term cognitive impairment with increased inflammation and apoptosis in the brain. Gelsolin, an actin-binding protein with capping and severing activities, plays a crucial role in the septic response. We investigated if gelsolin infusion could attenuate neural damage in burned mice.MethodsMice with 15% total body surface area burns were injected intravenously with bovine serum albumin as placebo (2 mg/kg), or with low (2 mg/kg) or high doses (20 mg/kg) of gelsolin. Samples were harvested at 8, 24, 48 and 72 hours postburn. The immune function of splenic T cells was analyzed. Cerebral pathology was examined by hematoxylin/eosin staining, while activated glial cells and infiltrating leukocytes were detected by immunohistochemistry. Cerebral cytokine mRNAs were further assessed by quantitative real-time PCR, while apoptosis was evaluated by caspase-3. Neural damage was determined using enzyme-linked immunosorbent assay of neuron-specific enolase (NSE) and soluble protein-100 (S-100). Finally, cerebral phospho-ERK expression was measured by western blot.ResultsGelsolin significantly improved the outcomes of mice following major burns in a dose-dependent manner. The survival rate was improved by high dose gelsolin treatment compared with the placebo group (56.67% vs. 30%). Although there was no significant improvement in outcome in mice receiving low dose gelsolin (30%), survival time was prolonged against the placebo control (43.1 ± 4.5 h vs. 35.5 ± 5.0 h; P < 0.05). Burn-induced T cell suppression was greatly alleviated by high dose gelsolin treatment. Concurrently, cerebral abnormalities were greatly ameliorated as shown by reduced NSE and S-100 content of brain, decreased cytokine mRNA expressions, suppressed microglial activation, and enhanced infiltration of CD11b+ and CD45+ cells into the brain. Furthermore, the elevated caspase-3 activity seen following burn injury was remarkably reduced by high dose gelsolin treatment along with down-regulation of phospho-ERK expression.ConclusionExogenous gelsolin infusion improves survival of mice following major burn injury by partially attenuating inflammation and apoptosis in brain, and by enhancing peripheral T lymphocyte function as well. These data suggest a novel and effective strategy to combat excessive neuroinflammation and to preserve cognition in the setting of major burns.

2011-12-01·American Journal of Physiology-Lung Cellular and Molecular Physiology2区 · 医学

An albumin-associated PLA₂-like activity inactivates surfactant phosphatidylcholine secreted from fetal type II pneumocytes

2区 · 医学

Article

作者: Cake, Max H. ; Damas, Jolanta E.

Type II pneumocytes are responsible for the synthesis and secretion of pulmonary surfactant, which reduces surface tension in lung alveoli, thus decreasing their tendency to collapse during expiration. For this effect to be sustained, the integrity of the surface-active components of surfactant must be maintained. This study has shown that, when cultured type II pneumocytes are exposed to lipoprotein-free serum (LFS), the level of lyso-phosphatidylcholine (lyso-PC) in the secreted surfactant phospholipids is markedly elevated with a concomitant decline in the level of phosphatidylcholine (PC). This effect is the result of hydrolysis of surfactant PC by a phospholipase A2(PLA2)-like activity present within serum. Anion-exchange chromatography, gel filtration chromatography and preparative electrophoresis of human LFS have shown that this PLA2-like activity coelutes with albumin and is biochemically distinct from the secretory form of PLA2. Furthermore, specific inhibitors of PLA2such as p-bromophenacyl bromide, aristolochic acid, and palmitoyl trifluoromethyl ketone do not inhibit this activity of serum. Commercially purified human serum albumin fraction V and recombinant human serum albumin (rHSA) are almost as effective as LFS in enhancing the level of lyso-PC in the media. The latter finding implies that rHSA directly generates lyso-PC from secreted PC and suggests that this PLA2-like activity may be an intrinsic attribute of albumin.

2011-09-01·Journal of Controlled Release1区 · 医学

Human serum albumin–thioredoxin fusion protein with long blood retention property is effective in suppressing lung injury

1区 · 医学

Article

作者: Yu Ishima ; Victor Tuan Giam Chuang ; Hiroshi Watanabe ; Masato Furukawa ; Kazuaki Taguchi ; Masaki Otagiri ; Toru Maruyama ; Ryota Tanaka

Thioredoxin (Trx) is a redox-active protein with anti-inflammatory effects but with a short half life of 1 h. Genetic fusion of Trx to human serum albumin (HSA) extended its half life without causing significant loss of its biological activities. HSA-Trx caused a decrease in the number of cells in brochoalveolar lavage fluid, the wet/dry ratio and the inflammation at the respiratory tract of the ovalbumin (OVA) induced lung injury model mouse. Three intraperitoneal doses of Trx alone produced the same extent of suppression of those three detrimental effects of OVA as one intravenous dose of HSA-Trx. Inhibition experiments confirmed that reactive oxygen species (ROS) and reactive nitrogen species (RNS) involved in the progression of the injury. HSA-Trx inhibited the production of ROS as confirmed in the EPR experiment, but lung tissue staining suggested that induced nitrogen oxide synthase (iNOS) was not suppressed by the fusion protein. Instead, the production of nitrotyrosine, 8-nitro-cGMP, and 8-hydroxy-2'-deoxyguanosine downstream to the iNOS has been inhibited. This suggested that HSA-Trx produced lung protection effect via different mechanisms from Trx alone. HSA-Trx retains the biological properties of Trx thus has great potential in treating oxidative stress related diseases.

100 项与人血清白蛋白（CSL Bering）相关的药物交易

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