Activation of Microglyocytes in the Anterior Horns of Rat Spinal Cord after Administration of Bacterial Lipopolysaccharide

Bulletin of Experimental Biology and Medicine - We studied the reaction of the microglia of the anterior horns of the rat spinal cord to intraperitoneal administration of bacterial LPS....     

Haematological Changes in the Tammar Wallaby (Macropus eugenii) Following Intraperitoneal Administration of Lipopolysaccharide

Intraperitoneal injection of lipopolysaccharide promoted a cellular haematological response in the peripheral blood of tammar wallabies. The changes in the treated wallabies were characterised by a decrease in the total leucocyte concentration from the baseline value at the 2 and 4h time-points and a mild increase in neutrophil concentration at 24h. Morphological changes in neutrophils including: increased numbers of neutrophils with a hyposegmented nucleus and cytoplasmic abnormalities were evident. No significant changes were observed in the fibrinogen concentration or serum electrophoretograms. As the changes in leucocyte concentration of tammar wallabies administered LPS were transient and mild, assessment of leucocyte morphology should be included in any laboratory investigations of macropodid health. Correspondence and offprint requests to: P. Clark, School of Clinical Sciences, Division of Veterinary and Biomedical Sciences, Murdoch University, South St, Murdoch, Western Australia, 6150. e-mail: pclark@murdoch.edu.au     

伸长细胞移植促进成年大鼠脊髓再生修复的研究

目的探讨采用体外培养的伸长细胞(Tanycytes,TAs)移植治疗大鼠脊髓损伤的可行性。方法将体外培养的TAs标记后,移植入全横断脊髓损伤大鼠。实验大鼠共分5组:A.单纯TAs细胞移植组,B.TAs细胞加壳聚糖载体移植组,C.壳聚糖载体移植组,D.单纯损伤组,E.假手术组。移植后通过BBB评分法评价大鼠的运动功能恢复情况,并且通过光学显微镜观察移植细胞的存活、迁移和损伤脊髓的修复情况,以及观察大鼠脑区神经元存活状况。结果与对照组相比,TAs移植促进了脊髓损伤局部结构的修复和大鼠下肢运动功能的恢复;移植组可在脑皮质观察到HRP逆行标记神经元;对照组皮质感觉运动区和红核神经元密度小于移植组,差异有显著意义。结论TAs移植可促进损伤脊髓轴突的再生、促进大鼠后肢运动功能的改善。     

Lipopolysaccharide Protection from Oxygen Toxicity: Effect on Rat Pulmonary Selectins

Sublethal doses of LPS result in increased tolerance to high concentrations of oxygen and this is associated with decreased pulmonary inflammation in a rat model. To investigate the mechanism of decreased neutrophil influx into the lung in this model, we measured levels of mRNA in the lung for the endothelial adhesion molecules, E-selectin and P-selectin. Immunostaining for E-selectin protein was also done in rat lungs, as well as measurement of soluble L-selectin in the blood. These levels were measured in the lungs of adult rats injected with 0.5 mg/kg LPS or placebo at 0 and 24 h and exposed to > 95% O2 for 60 h. Oxygen exposure resulted in significant increases in both E- and P-selectin mRNA and in E-selectin protein after 60 h. LPS resulted in an early rise in E-selectin protein followed by a decline to less than control (saline/O2) levels at 60 h. Messenger RNA for E-selectin followed a similar trend, although there were no differences at 60 h between LPS and control groups exposed to O2. P-selectin mRNA expression did not significantly differ between LPS and control O2 groups. Soluble L-selectin levels decreased by 6 h after LPS infusion and were significantly lower than saline/O2 controls through 24 h, suggesting binding to endothelium. In conclusion, the decrease in E-selectin expression on the surface of pulmonary endothelium after LPS could contribute to decreased inflammation in this model of oxygen toxicity. Soluble L-selectin may serve a further anti-inflammatory role after LPS infusion by binding to pulmonary endothelium.     

Immunomodulatory Effects of Bacterial Lipopolysaccharide

Abstract

The most easily discernible and characteristic result of interaction of LPS with the immune system are the activation of B cells to divide and/or synthesize and secrete immunoglobulin. LPS as an antigen or carrier for chemically defined haptens induces a T independent antibody response, while antibody responses to unrelated T dependent antigens are modulated by LPS. Such regulation can be explained both by increased susceptibility of B cells to regulation after interaction with LPS, and increased activity of regulatory cells after their interaction with LPS. Studies of these mechanisms have exploited the availability of several strains of mice which are genetically poorly responsive to LPS and thus have helped to define the genetic basis of LPS responses. In addition, these studies have demonstrated the existence of other bacterial cell wall components which have some of the immunological properties of LPS but are not susceptible to the same genetic control. Future studies on the molecular nature of the interaction of LPS with target cells and the biochemical basis of cell triggering should yield interesting information on the cell biology of cell activation.     

Immunomodulatory Effects of Bacterial Lipopolysaccharide

The most easily discernible and characteristic result of interaction of LPS with the immune system are the activation of B cells to divide and/or synthesize and secrete immunoglobulin. LPS as an antigen or carrier for chemically defined haptens induces a T independent antibody response, while antibody responses to unrelated T dependent antigens are modulated by LPS. Such regulation can be explained both by increased susceptibility of B cells to regulation after interaction with LPS, and increased activity of regulatory cells after their interaction with LPS. Studies of these mechanisms have exploited the availability of several strains of mice which are genetically poorly responsive to LPS and thus have helped to define the genetic basis of LPS responses. In addition, these studies have demonstrated the existence of other bacterial cell wall components which have some of the immunological properties of LPS but are not susceptible to the same genetic control. Future studies on the molecular nature of the interaction of LPS with target cells and the biochemical basis of cell triggering should yield interesting information on the cell biology of cell activation.     

Regulation of β-Chemokine mRNA Expression in Adult Rat Astrocytes by Lipopolysaccharide, Proinflammatory and Immunoregulatory Cytokines

The progression of cutaneous leishmaniasis is controlled largely by cell-mediated immunity. Two subpopulations of CD4⁺ T cells exist that control healing or immunopathology of murine and, perhaps, human leishmaniasis. To better understand the immunological pathways controlling outcome of the human disease, we analysed the pattern of tumour necrosis factor (TNF) and interleukin-2 (IL-2), both of which were present in the sera of humans with active or healed chiclero's ulcer, in relation to the development of delayed-type hypersensitivity (DTH) responses and leucocyte counts in peripheral blood. Increased serum levels of IL-2 and TNF-α were apparent only in individuals with active lesions. All individuals with localized cutaneous leishmaniasis developed a strong DTH. The number of T cells was lower in the blood of diseased individuals and the CD4/CD8 ratio was reduced (from 1.5 to 1.0) when compared with the control group. However, diseased and recently cured individuals developed eosinophilia. We conclude that important alterations of the immune response exists in humans suffering from this normally self-healing infection.     

Effect of Prolonged Monoclonal Antibody Administration on Cardiac Allograft Survival in the Rat

After heterotopic cardiac transplantation in the rat, monoclonal antibodies (MoAb) specific for rat T-cell subsets were administered until rejection. Across combined major histocompatibility complex (MHC) and non-MHC differences (WF to Lew) and isolated non-MHC differences (WF to Lew.1W) cardiac allografts were rapidly rejected in unmodified hosts (7.7 +/- 1.0 days and 12.2 +/- 0.8 days respectively). Across combined MHC and non-MHC differences, administration of MoAb OX-19 (pan T-cell) on days -1, 0, and 1 (where day 0 was the day of transplantation) and alternate days thereafter until rejection significantly prolonged allograft survival (28.5 +/- 10.2 days, P less than 0.01). Administration of MoAb W3/25 (helper T cell) and MoAb OX-39 (interleukin 2 (IL-2) receptor) prolonged allograft survival (11.3 +/- 2.6 days, P less than 0.05 and 13.3 +/- 2.0 days, P less than 0.01 respectively), whereas MoAb OX-8 (cytotoxic/suppressor T cell) administration had no effect on allograft survival. In contrast, across non-MHC differences (WF to Lew.1W) administration of MoAb OX-8 markedly prolonged allograft survival (85, greater than 100 x 3 days) whereas MoAb W3/25 administration had no effect. The effect of MoAb administration on lymphocyte subsets at rejection was assessed by flow cytometry. The relationship between depletion of targeted T-cell subsets and graft survival was variable. Across both combined MHC and non-MHC and isolated non-MHC differences MoAb OX-8 administration resulted in a marked reduction of OX-8+ cells at rejection with no prolongation of graft survival in the former and indefinite graft survival in the latter. In contrast, OX-19 administration resulted in prolonged graft survival but at rejection there were significant numbers of OX-19+ cells present. Administration of MoAb W3/25 failed to affect a significant reduction in W3/25+ cells, but allograft survival was nonetheless prolonged.     

Effects of Ethanol and Lipopolysaccharide on the Sphingomyelin Cycle in Rat Hepatocytes

Lipopolysaccharide toxin added to primary hepatocyte culture slightly modified the basal concentrations of ³H-serine-labeled sphingomyelin, sphingosine, and ceramide. Ethanol reduced the levels of sphingomyelin and sphingosine by 20–25 and 15–20%, respectively, but increased ceramide content by 7–17%. Tumor necrosis factor reduced the concentrations of sphingomyelin and sphingosine, but did not modify the content of ceramide. Combined treatment with lipopolysaccharide toxin and ethanol potentiated the effect of alcohol. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 12, pp. 660-662, December, 2008     

Changes in Behavior and the Expression of Ionotropic Glutamate Receptor Genes in the Brains of Adult Rats after Neonatal Administration of Bacterial Lipopolysaccharide

Neuroscience and Behavioral Physiology - Many studies have shown that early experience, particularly of neonatal infections, has a role in forming high anxiety levels in later life. One of the...     

Bacterial Lipopolysaccharide: Oral Route for Interferon Production in Mice

Bacterial lipopolysaccharide given orally to mice in relatively small amounts produces significant amounts of circulating interferon.     

Effective Inhibition of Cardiolipin-Binding Antibodies in Gram-Negative Infections by Bacterial Lipopolysaccharide

Anticardiolipin antibodies (ACA) were detected by solid-phase enzyme immunoassay in the majority of sera from patients with Gram-positive and Gram-negative bacterial infections. The response involved all the major immunoglobulin classes IgG, IgM, and IgA. The specificity of the ACA was studied in competitive inhibition experiments with three putative antigens: cardiolipin, lipopolysaccharide (LPS) isolated from Salmonella minnesota, strain Re 595, and synthetic Escherichia coli lipid A. The binding of IgG class ACA from the sera of five patients with Gram-negative infections was effectively inhibited by LPS, whereas 100-fold more cardiolipin was required for comparable inhibition. Pure lipid A was a less effective inhibitor of anticardiolipin activity than LPS. This pattern of reactivity was not seen in sera from patients with Gram-positive infections, syphilis, or systemic lupus erythematosus. Our findings suggest that cardiolipin may not be the inducing antigen for the cardiolipin-binding antibodies that develop in Gram-negative infections.     

The Effect of Complement Depletion on Bacterial Lipopolysaccharide (LPS)-Induced Hemodynamic and Hematologic Changes in the Rhesus Monkey

Lipopolysaccharide (LPS) isolated from Salmonella minnesota R595 or from Escherichia coli 0111:B4 induces hypotension in rhesus monkeys with normal complement levels. This hypotension is accompanied by decreased total peripheral resistance. The depletion of C3 and terminal complement components by prior intraperitoneal administration of the anticomplementary protein cobra factor did not alter the hemodynamic changes which occur following the rapid injection of 5 mg/kg of R595 LPS, the infusion of 500 microgram/kg of R595 LPS, or the injection of 500 microgram/kg of 0111:B4 LPS. We conclude that the LPS-induced hemodynamic changes in the subhuman primate are medicated by pathways which do not require the participation of C3. The kinetics and extent of the neutropenia and thrombocytopenia resulting from the injection of 0111:B4 or R595 LPS were not latered by prior depletion of greater than 95% of the plasma C3.     

Enhanced Effect of Repeated Administration of Bacterial Vaccine Against Viral Respiratory Infection

Administration of a standard bacterial vaccine (SBV) affords some protection against influenza infection in mice if given 4 to 5 h before inoculation of the virus. This effect was enhanced by repeated injections of SBV 7 and 14 days earlier, as measured by the length of survival, mortality rate, development of gross pneumonia, and virus multiplication in the lungs. Serum interferon levels were likewise enhanced by immunization with SBV, which may, at least in part, explain the increased preventive effect.     

Comparison of Interleukin 1 Release and Interleukin 1 mRNA Expression of Human Monocytes Activated by Bacterial Lipopolysaccharide or Synthetic Lipid A

Several of the biological effects of bacterial lipopolysaccharide (LPS) can be induced by the lipid A part of the molecule. Here we show that in human peripheral blood monocytes, synthetic E. coli lipid A is as effective as the whole LPS molecule in inducing the production of interleukin 1 (IL-1) bioactivity which remains associated to the cells (i.e. IL-1 alpha). In contrast, LPS- but not lipid A-stimulated cells released the bioactive IL-1 produced into the culture supernatant (mainly IL-1 beta). Northern blotting analysis demonstrated, however, that LPS and lipid A are equally effective in inducing the accumulation of IL-1 alpha and IL-1 beta mRNA. These data support the hypothesis that induction of IL-1 biosynthesis and activation of the secretory mechanism for IL-1 are independent phenomena.     

The Effect of Progesterone and of Insulin Administration on Regional Adipose Tissue Cellularity in the Rat

Female rats were given progesterone in a high and a low dose or insulin by injection. Both hormones caused hyperinsulinemia and an elevated body weight, explainable by increased fat tissue weight, which in turn was due to an increased fat cell size. There was a regional specificity of these effects for both procedures. It was therefore concluded that adipose tissue does not react as a homogenous tissue to different stimuli. Although not definitely conclusive because of difference in the degree of hyperinsulinemia the results also indicate that the effects of insulin are primarily exerted on the small fat cells of the subcutaneous region while progesterone increased the size of the larger parametrial fat cells.