Search

Acute lung injury (ALI) is a serious clinical disease. Rotundic acid (RA), a natural ingredient isolated from Ilex rotunda Thunb, exhibits multiple pharmacological activities. However, RA's therapeutic effect and mechanism on ALI remain to be elucidated. The present study aimed to further clarify its regulating effects on inflammation in vitro and in vivo. Our results indicated that RA significantly inhibited the overproduction of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). RA decreased ROS production and calcium influx. In addition, RA inhibited the activation of PI3K, MAPK, and NF-κB pathways and enhanced the activity of nuclear factor E2-related factor 2 (Nrf2) signaling. The cellular thermal shift assay and docking results indicated that RA bind to TLR4 to block TLR4 dimerization. Furthermore, RA pretreatment effectively inhibited ear edema induced by xylene and LPS-induced endotoxin death and had a protective effect on LPS-induced ALI. Our findings collectively indicated that RA has anti-inflammatory effects, which may serve as a potential therapeutic option for pulmonary inflammation.

Cyclooxygenase‐2 (COX‐2), a key enzyme in arachidonic acid metabolism, is involved in several cancers, including osteosarcoma. The prognostic significance of COX‐2 in osteosarcoma remains controversial. This study was to analyze the potential clinical and prognostic effects of COX‐2 protein expression in patients with osteosarcoma. Eligible articles were searched via online databases. The combined odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were calculated using the random‐effects model. Trial sequential analysis (TSA) was applied to analyze the required information size and determine the reliability of the evidence. Twenty‐three studies on COX‐2 expression were identified, which included a total of 1084 patients with malignant osteosarcoma and 247 patients with benign osteochondroma. COX‐2 protein expression in osteosarcoma was higher than in benign osteochondroma (OR = 7.66, P 0.1), but was significantly associated with tumor grade (high grade vs. low grade: OR = 4.81, P

Although the genotype-phenotype for familial medullary thyroid carcinoma (FMTC) is well studied, only few low susceptibility risk loci were identified for familial non-medullary thyroid carcinoma (FNMTC). The aim of this study is to screen and identify high-penetrate genes for FNMTC. A total of 34 families with more than two first-degree relatives diagnosed as papillary thyroid cancer without other familial syndrome were recruited. Whole exome and target gene sequencing were performed for candidate variants. These variants were screened and analyzed with ESP6500, ExAC, 1000 genomes project, and the Cancer Genome Atlas (TCGA) with SIFT score and Polyphen2 prediction. Finally, we identified recurrent genetic mutation of MAP2K5 variants c.G961A and c.T1100C (p. A321T and p.M367 T) as susceptibility loci for FNMTC. The frequencies of MAP2K5 c.G961A and c.T1100C were found, 0.0385 and 0.0259 in FNMTC and 0 and 0.00022523 in healthy Chinese controls (n = 2200, P < 0.001), respectively. Both variants were located in the protein kinase domain. The functional study showed that MAP2K5 A321T or M367 T could consistently phosphorylate downstream protein ERK5 on site Ser731 + Thr733 or Ser496, promoting nuclear translocation and subsequently altering target gene expressions. Our data revealed that MAP2K5 variants A321T or M367 T can activate MAP2K5-ERK5 pathway, alter downstream gene expression, and subsequently induce thyroid epithelial cell malignant transformation. While classic MAP2K1/2(MEK1/2)-ERK1/2 signaling is well known for driving sporadic NMTC, our research indicated that MAP2K5 (MEK5) is a susceptibility gene for FNMTC. These findings highlight the potential application of MAP2K5 for molecular diagnosis as well as early prevention.

Peroxisome proliferator-activated receptor γ (PPARγ) is expressed in various types of human cancer cells including leukaemia cells, and activation of PPARγ can inhibit cancer cell growth. However, whether PPARγ is expressed in Jurkat cells, a human T-lymphocyte leukaemia cell line, and whether activation of PPARγ affects cell biological behaviors remains to be clarified. In this study, we investigated the effect of a PPARγ activator rosiglitazone, under clinically relevant pharmacological concentrations, on the growth and apoptosis of Jurkat cells in vitro and explored the possible mechanism. Metformin was also included as a positive control for the anti-proliferative and pro-apoptotic effects. We found that PPARγ mRNA was transcribed in Jurkat cells. Treatment with rosiglitazone (5 µM, 10 µM, and 20 µM) or metformin (1 mM and 10 mM) inhibited cell proliferation, and induced cell cycle arrest at G0/G1 or S phase, respectively, in a dose-dependent manner. Although metformin significantly upregulated the protein levels of the pro-apoptotic markers cleaved-caspase 3 and Bax in Jurkat cells, rosiglitazone did not have such an effect. Moreover, rosiglitazone significantly upregulated the level of PPARγ, and downregulated the expression of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R) in a dose-dependent manner. Our data indicate that rosiglitazone has an anti-proliferative effect in Jurkat cells, which may be at least partly mediated via downregulating IR and IGF-1R expression. Therefore, rosiglitazone may have a potential role not only for management of hyperglycaemia but also for control of tumor progression in patients with T-lymphocyte leukaemia and diabetes.

Background and Purpose Isoacteoside (is a phenylethanoid isolated from Monochasma savatieri Franch. ex Maxim., which is an anti-inflammatory herb widely used in traditional Chinese medicine. However, the exact mechanism of the anti-inflammatory activity of isoacteoside is not completely understood. In this study, its anti-inflammatory mechanism was elucidated in mouse macrophages. Experimental Approach The expression of the NF-κB pathway, MAPK pathway, iNOS, TNF-α, IL-6 and IL-1β was evaluated using Western blotting, quantitative real-time PCR or ELISA. TLR4 dimerization was determined by transfecting HEK293T cells with TLR4 plasmids. The in vivo anti-inflammatory effect of isoacteoside was determined using mouse models of xylene-induced ear oedema, LPS-induced endotoxic shock and LPS-induced endotoxaemia-associated acute kidney injury (AKI). Key Results Isoacteoside suppressed COX-2, iNOS, TNF-α, IL-6 and IL-1β expression. Furthermore, isoacteoside attenuated the LPS-induced transcriptional activity of NF-κB by decreasing the levels of phosphorylated IκB-α and IKK and NF-κB/p65 nuclear translocation. In addition, isoacteoside inhibited LPS-induced transcriptional activity of AP-1 by reducing the levels of phosphorylated JNK1/2 and p38MAPK. Isoacteoside blocked LPS-induced TLR4 dimerization, resulting in a reduction in the recruitment of MyD88 and TIR-domain-containing adapter-inducing interferon-β (TRIF) and the phosphorylation of TGF-β-activated kinase-1 (TAK1). Pretreatment of mice with isoacteoside effectively inhibited xylene-induced ear oedema and LPS-induced endotoxic death and protected against LPS-induced AKI. Conclusions and Implications Isoacteoside blocked TLR4 dimerization, which activates the MyD88–TAK1–NF-κB/MAPK signalling cascades and TRIF pathway. Our data indicate that isoacteoside is a potential lead compound for the treatment of inflammatory diseases.

Previous reports showed that nepetoidin B (NTB), a natural product isolated from many herbs, has anti-fungal and anti-bacterial effects. In this study, the antiinflammatory effect of NTB was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic effect of NTB and LPS was determined by MTT assay. The nitric oxide (NO) production was detected by Griess assay. The TNF-α and IL-6 levels were determined by enzyme-linked immunosorbent assay kits. Protein expressions were tested by western blotting. The transcription activity of inducible nitric oxide synthase (iNOS) was detected by luciferase assay. Immunofluorescence assay was used to observe the visualization of NF-κB/p65 nuclear translocation. NTB and LPS showed no obvious cytotoxic effect on RAW 264.7 cells. NTB remarkably inhibited LPS-induced NO and TNF-α secretion in a concentration-dependent manner while showed no significant effect on IL-6 secretion. NTB inhibited LPS-induced iNOS protein expression and transcription activity without affecting cyclooxygenase-2. Furthermore, NTB suppressed LPS-stimulated NF-κB/p65 phosphorylation and nuclear translocation. In addition, NTB significantly inhibited LPS-induced phosphorylation of JNK1/2 and p38MAPK without affecting ERK1/2. LPS-induced inhibition of mitogen-activated protein kinase phosphatase-5 (MKP-5) was completely reversed by NTB. In conclusion, these results suggested that NTB inhibited LPS-stimulated NO production possibly via modulation of iNOS mediated by MKP-5/NF-κB pathways in RAW 264.7 cells. Copyright © 2017 John Wiley & Sons, Ltd.

Gynura procumbens (Lour.) Merr. is traditionally used as a raw material for making dumplings or steamed stuffed buns, and its fresh leaves are boiled with water for tea. Herein, we established an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) combined with characteristic ion filtration (CIF) strategy to rapidly screen active ingredients with antioxidant and anti-inflammatory properties in G. procumbens. This strategy involved screening the active part of G. procumbens using antioxidation and anti-inflammatory activity assays; discovering the active compounds by speculating on the active site's chemical composition by UHPLC-Q-TOF-MS/MS plus CIF; and verifying the active compounds' activities. The ethyl acetate extract (EEAF) of G. procumbens was the major active site. Eighty-one compounds were identified from the EEAF using UHPLC-Q-TOF-MS/MS plus CIF. Furthermore, polyphenols such as cynarine, isochlorogenic acids A and isochlorogenic acids C have excellent antioxidizing and anti-inflammatory activities. This study provides a practical strategy for rapid in vitro screening of the antioxidizing and anti-inflammatory activities of traditional vegetables and herbs and identification of active ingredients.

We developed a reverse-time migration scheme that can image regions with rugged topography without requiring any approximations by adopting an irregular, unstructured-grid modelling scheme. This grid, which can accurately describe surface topography and interfaces between high-velocity-contrast regions, is generated by Delaunay triangulation combined with the centroidal Voronoi tessellation method. The grid sizes vary according to the migration velocities, resulting in significant reduction of the number of discretized nodes compared with the number of nodes in the conventional regular-grid scheme, particularly in the case wherein high near-surface velocities exist. Moreover, the time sampling rate can be reduced substantially. The grid method, together with the irregular perfectly matched layer absorbing boundary condition, enables the proposed scheme to image regions of interest using curved artificial boundaries with fewer discretized nodes. We tested the proposed scheme using the 2D SEG Foothill synthetic dataset.

SUMMARY This study documents the first attempt to extend the singular boundary method (SBM), a novel meshless boundary collocation method, for the solution of three-dimensional (3D) elasticity problems. The SBM involves a coupling between the regularized boundary element method (BEM) and the method of fundamental solutions (MFS). The main idea here is to fully inherit the dimensionality and stability advantages of the former and the meshless and integration-free attributes of the later. This makes it particularly attractive for problems in complex geometries and three dimensions. Four benchmark 3D problems in linear elasticity are well studied to demonstrate the feasibility and accuracy of the proposed method. The advantages, disadvantages and potential applications of the proposed method, as compared with the FEM, BEM and MFS, are also examined and discussed. This article is protected by copyright. All rights reserved.

Objectives We evaluated the protective effects of protein phosphatase 2A (PP2A)/tristetraprolin (TTP) against brain edema in a rat model of cerebral hemorrhage, bleeding in the brain that occurs in tissues and ventricles. TTP is a well‐known mRNA‐binding protein and essential regulatory molecule for gene expression. Methods Cerebral hemorrhage was induced in male albino rats divided into four homogeneous groups: normal control (I), control (II), PP2A siRNA (III), and scrambled siRNA (IV). Neurological scores, caspase‐3 mRNA and protein expression, PP2A and TTP protein expression, apoptosis, and water content in the brain were determined. Results The neurological score decreased substantially to 8.2 in rats in which cerebral hemorrhage was induced and was further reduced to 7.4 and 7.7 in groups III and IV, respectively. Caspase‐3 expression increased significantly by 90% in group II and by 26.9% in group III. Apoptosis increased by 26.1% in rats in which cerebral hemorrhage was induced and increased considerably by 35.3% and 33.4% in groups III and IV, respectively. PP2A and TTP protein expression increased significantly by 87% and 59%, as compared to their respective sham controls. However, PP2A and TTP siRNA treatment reduced the protein expression of PP2A and TTP in groups III and IV. The water content in the brain increased significantly by 77.4% in rats in which cerebral hemorrhage was induced (group II), as compared to the sham group. The water content in the brain increased by 84.1% and 78.7% in groups III and IV, respectively. Conclusion Taken together, these data indicate that TTP has a protective role against brain edema by reducing inflammation, apoptosis, and water content in the brain at 48 hr after cerebral hemorrhage. Our findings may be useful for developing important approaches to treating brain injury.

Klebsiella pneumoniae is one of the most common pathogens in nosocomial infections and is becoming increasingly multidrug-resistant. However, the underlying molecular pathogenesis of this bacterium remains elusive, limiting the therapeutic options. Understanding the mechanism of its pathogenesis may facilitate the development of antibacterial therapeutics. Here, we show that Lyn, a pleiotropic Src tyrosine kinase, is involved in host defense against K. pneumoniae (Kp) by regulating phagocytosis process and simultaneously downregulating inflammatory responses. Using acute infection mouse models, we observed that lyn−/− mice were more susceptible to Kp with increased mortality and severe lung injury compared with wild-type mice. Kp infected-lyn−/− mice exhibited elevated inflammatory cytokines (IL-6 and TNF-α), and increased superoxide in the lung and other organs. In addition, the phosphorylation of p38 and NF-κB p65 subunit increased markedly in response to Kp infection in lyn−/− mice. We also demonstrated that the translocation of p65 from cytoplasm to nuclei increased in cultured murine lung epithelial cells by Lyn siRNA knockdown. Furthermore, lipid rafts clustered with activated Lyn and accumulated in the site of Kp invasion. Taken together, these findings revealed that Lyn may participate in host defense against Kp infection through the negative modulation of inflammatory cytokines.

Although uncontrolled inflammatory response plays a central role in the pathogenesis of acute lung injury (ALI), the precise molecular mechanisms underlying the development of this disorder remain poorly understood. SOCS3 is an important negative regulator of IL-6-type cytokine signaling. SOCS3 is induced in lung during LPS-induced lung injury, suggesting that generation of SOCS3 may represent a regulatory product during ALI. In the current study, we created mice lacking SOCS3 expression in macrophages and neutrophils (LysM-cre SOCS3fl/fl). We evaluated the lung inflammatory response to LPS in both LysM-cre SOCS3fl/fl mice and the wild-type (WT) mice (SOCS3fl/fl). LysM-cre SOCS3fl/fl mice displayed significant increase of the lung permeability index (lung vascular leak of albumin), neutrophils, lung neutrophil accumulation (myeloperoxidase activity), and proinflammatory cytokines/chemokines in bronchial alveolar lavage fluids compared to WT mice. These phenotypes were consistent with morphological evaluation of lung, which showed enhanced inflammatory cell influx and intra-alveolar hemorrhage. We further identify the transcription factor, CCAAT/enhancer-binding protein (C/EBP) δ as a critical downstream target of SOCS3 in LPS-induced ALI. These results indicate that SOCS3 has a protective role in LPS-induced ALI by suppressing C/EBPδ activity in the lung. Elucidating the function of SOCS3 would represent prospective targets for a new generation of drugs needed to treat ALI.—Yan, C., Ward, P. A., Wang, X., Gao, H. Myeloid depletion of SOCS3 enhances LPS-induced acute lung injury through CCAAT/enhancer binding protein δ pathway.

Caveolin-1 (Cav1) is a structural protein of caveolae. Although Cav1 is associated with certain bacterial infections, it is unknown whether Cav1 is involved in host immunity against Klebsiella pneumoniae, the third most commonly isolated microorganism from bacterial sepsis patients. Here, we showed that cav1 knockout mice succumbed to K. pneumoniae infection with markedly decreased survival rates, increased bacterial burdens, intensified tissue injury, hyperactive proinflammatory cytokines, and systemic bacterial dissemination as compared with WT mice. Knocking down Cav1 by a dominant negative approach in lung epithelial MLE-12 cells resulted in similar outcomes (decreased bacterial clearance and increased proinflammatory cytokine production). Furthermore, we revealed that STAT5 influences the GSK3β-β-catenin-Akt pathway, which contributes to the intensive inflammatory response and rapid infection dissemination seen in Cav1 deficiency. Collectively, our findings indicate that Cav1 may offer resistance to K. pneumoniae infection, by affecting both systemic and local production of proinflammatory cytokines via the actions of STAT5 and the GSK3β-β-catenin-Akt pathway.

Growing evidences indicate that Ly-GDI, an inhibitory protein of Rho GTPases, plays an essential role in regulating actin cytoskeletal alteration which is indispensible for the process such as phagocytosis. However, the role of Ly-GDI in inflammation remains largely unknown. In the current study, we found that Ly-GDI expression was significantly decreased in the IgG immune complex-injured lungs. To determine if Ly-GDI might regulate the lung inflammatory response, we constructed adenovirus vectors that could mediate ectopic expression of Ly-GDI (Adeno-Ly-GDI). In vivo mouse lung expression of Ly-GDI resulted in a significant attenuation of IgG immune complex-induced lung injury, which was due to the decreased pulmonary permeability and lung inflammatory cells, especially neutrophil accumulation. Upon IgG immune complex deposition, mice with Ly-GDI over-expression in the lungs produced significant less inflammatory mediators (TNF-α, IL-6, MCP-1, and MIP-1α) in bronchoalveolar lavage fluid when compared control mice receiving airway injection of Adeno-GFP. Mechanically, IgG immune complex-induced NF-κB activity was markedly suppressed by Ly-GDI in both alveolar macrophages and lungs as measured by luciferase assay and electrophoretic mobility shift assay. These findings suggest that LyGDI is a critical regulator of inflammatory injury after deposition of IgG immune complexes and that it negatively regulates the lung NF-κB activity.

An electrochemical DNA biosensor was fabricated by immobilizing DNA probe on aluminum ion films that were electrodeposited on the surface of the stearic acid-modified carbon paste electrode (CPE). DNA immobilization and hybridization were characterized with cyclic voltammetry (CV) by using methylene blue (MB) as indicator. MB has a couple of well-defined voltammetric redox peaks at the CPE. The currents of redox peaks of MB decreased after depositing aluminum ion films on the CPE (Al(III)/CPE) and increased dramatically after immobilizing DNA probe (ssDNA/Al(III)/CPE). Hybridization of DNA probe led to a marked decrease of the peak currents of MB, which can be used to detect the target single-stranded DNA. The conditions for the preparation of Al(III)/CPE, and DNA immobilization and hybridization were optimized. The specific sequences related to bar transgene in the transgenic corn and the PCR amplification of CP4 epsps gene from the sample of transgenic roundup ready soybean were detected by differential pulse voltammetry (DPV) with this new electrochemical DNA biosensor. The difference between the peak currents of MB at ssDNA/Al(III)/CPE and that at hybridization DNA modified electrode (dsDNA/Al(III)/CPE) was applied to determine the Specific sequence related to the target bar gene with the dynamic range comprised between 1.0 X 10(-7) mol/L to 1.0 x 10(-4) mol/L. A detection limit of 2.25 x.10(-8) mol/L. of oligonucleotides can be estimated.

We have evaluated the hypothesis that cGMP may serve as an intracellular messenger regulating the viability of pancreatic beta-cells. A direct activator of soluble guanylyl cyclase, YC-1, caused a time- and dose-dependent loss of viability in clonal BRIN-BD11 beta-cells. This was accompanied by a rise in cGMP and was antagonised by Rp-8-pCPT-cGMPS, a selective inhibitor of protein kinase G (PKG). Reverse transcription polymerase chain reaction analysis confirmed that BRIN-BD11 cells (and human islets) express all three known isoforms of PKG (PKG-Ialpha, -Ibeta and II). Cell death induced by YC-1 was not sensitive to cell-permeable caspase inhibitors and was not accompanied by oligonucleosomal DNA fragmentation. The response was, however, inhibited by actinomycin D, suggesting that a transcription-dependent pathway of programmed cell death is involved in the actions of cGMP.

Efaroxan induces membrane depolarization by interaction with the pore forming subunit of the ATP-sensitive potassium channel, Kir6.2. However, this effect is not responsible for its full secretory activity. In this study we have used an anti-idiotypic approach to generate antibodies that recognize additional proteins that may be regulated by efaroxan in pancreatic β-cells. Using these antisera in an expression cloning strategy we have identified a monomeric GTP-binding protein, Rhes, as a potential target for regulation by imidazoline ligands. Rhes is shown to be expressed in β-cells and its expression is regulated by efaroxan under conditions when a structurally related molecule, KU14R, is ineffective. The results reveal that β-cells express Rhes and suggest that changes in the expression of this molecule may regulate the sensitivity of β-cells to imidazoline secretagogues. British Journal of Pharmacology (2002) 136, 31–36; doi:10.1038/sj.bjp.0704680

The hydrogen bonding complexes formed between the H2O and OH radical have been completely investigated for the first time in this study using density functional theory (DFT). A larger basis set 6-311++G(2d,2p) has been employed in conjunction with a hybrid density functional method, namely, UB3LYP/6-311++G(2d,2p). The two degenerate components of the OH radical 2Π ground electronic state give rise to independent states upon interaction with the water molecule, with hydrogen bonding occurring between the oxygen atom of H2O and the hydrogen atom of the OH radical. Another hydrogen bond occurs between one of the H atoms of H2O and the O atom of the OH radical. The extensive calculation reveals that there is still more hydrogen bonding form found first in this investigation, in which two or three hydrogen bonds occur at the same time. The optimized geometry parameter and interaction energy for various isomers at the present level of theory was estimated. The infrared (IR) spectrum frequencies, IR intensities, and vibrational frequency shifts are reported. The estimates of the H2O · OH complex's vibrational modes and predicted IR spectra for these structures are also made. It should be noted that a total of 10 stationary points have been confirmed to be genuine minima and transition states on the potential energy hypersurface of the H2O · HO system. Among them, four genuine minima were located. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002

Background Supported by the International Society for Translational Medicine (ISTM), Wenzhou Medical College and the First Affiliated Hospital of Wenzhou Medical College, the International Conference on Translational Medicine (ICTM) was held on October 22–23, 2011 in Wenzhou, China. Nearly 800 registrants attended the meeting, primarily representing institutes and hospitals in Europe, The United States of America, And Asia, and China. The meeting was chaired and organized by Dr. Xiangdong Wang, Xiaoming Chen, Richard Coico, Jeffrey M. Drazen, Richard Horton, Francesco M. Marincola, Laurentiu M. Popescu, Jia Qu and Aamir Shahzad. Findings The meeting focused on the communication of the need to foster translational medicine (TM) by building and broadening bridges between basic research and clinical studies at the international level. The meeting included distinguished TM experts from academia, the pharmaceutical and diagnostics industries, government agencies, regulators, and clinicians and provided the opportunity to identify shared interests and efforts for collaborative approaches utilizing cutting edge technologies, innovative approaches and novel therapeutic interventions. The meeting defined the concept of TM in its two‐way operational scheme and emphasized the need for bed to bench efforts based directly on clinical observation. Conclusions It was the meeting participants’ realization that the shared main goals of TM include breaking the separation between clinic practice and basic research, establishing positive feedback by understanding the basis of expected and unexpected clinical outcomes and accelerating basic research relevant to human suffering. The primary objectives of the meeting were two‐fold: to accelerate the two‐way translation by informing the participants representing the different disciplines about the state of art activities around TM approaches; and to identify areas that need to be supported by redirecting limited resources as well as identifying new sources of funding. This report summarizes key concepts presented during the meeting representing the state‐of‐art translational research and salient aspects of the ensuing discussions.

Delayed neutrophil apoptosis is characteristic of sepsis and may accentuate organ injury. It has been shown that phosphatidylinositol 3-kinase (PI3-K) and MAPK pathways provide survival signaling in neutrophils. In this study, we demonstrate that neutrophils isolated from septic rats are resistant to apoptosis in comparison to the cells from normal animals. In contrast to normal serum, septic sera induced strong phosphorylation of AKT and p44/42 in neutrophils obtained from normal rats, resulting in marked resistance of these cells to apoptosis. Protection from apoptosis by septic sera was completely abrogated by inhibition of PI3-K and partially diminished by MAP kinase (MEK) inhibition. Increased neutrophil survival in septic rats was associated with increased levels of Bcl-xL in neutrophils and decreased levels of Bim expression. In vivo blockade of C5a in CLP rats by anti-C5a antibody markedly restored the susceptibility of neutrophils to undergo apoptosis. C5a activated AKT and p44/42, and also enhan...