scholarly journals Recombinant Bactericidal/Permeability-Increasing Protein rBPI21 Protects against Pneumococcal Disease

2006 ◽  
Vol 75 (1) ◽  
pp. 342-349 ◽  
Author(s):  
Amit Srivastava ◽  
Heather Casey ◽  
Nathaniel Johnson ◽  
Ofer Levy ◽  
Richard Malley
Keyword(s):  
Pneumococcal Disease ◽  
Gram Negative Bacteria ◽  
Dependent Manner ◽  
Upper Respiratory Tract ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Murine Macrophages ◽  
Mouse Macrophages ◽  
Factor Alpha ◽  
Potential Interactions

ABSTRACT Bactericidal/permeability-increasing (BPI) protein has been shown to play an important role in innate immunity to gram-negative bacteria, by direct microbicidal as well as endotoxin-neutralizing action. Here we examined potential interactions between a recombinant 21-kDa bioactive fragment of BPI, rBPI21, and the gram-positive pathogen Streptococcus pneumoniae. rBPI21 bound to pneumococci and pneumolysin (Ply) in a direct and specific fashion. We observed an enhanced inflammatory response in mouse macrophages when rBPI21 was combined with killed pneumococci or supernatant from overnight growth of pneumococci. In addition, rBPI21 augmented the proapoptotic activity of Ply+ (but not Ply−) pneumococci in TLR4-defective murine macrophages (known to be defective also in their apoptotic response to pneumolysin) in a tumor necrosis factor alpha-dependent manner. rBPI21 also enhanced the association of pneumococci with murine macrophages. In a model of invasive pneumococcal disease in TLR4-defective mice, the intranasal administration of rBPI21 following intranasal inoculation of Ply+ pneumococci both enhanced upper respiratory tract cell apoptosis and prolonged survival. We have thus discovered a novel interaction between pneumococcus and rBPI21, a potent antimicrobial peptide previously considered to target only gram-negative bacteria.

scholarly journals Comparable Endotoxic Properties of Lipopolysaccharides Are Manifest in Diverse Clinical Isolates of Gram-Negative Bacteria

2000 ◽  
Vol 68 (4) ◽  
pp. 1899-1904 ◽  
Author(s):  
Michael Luchi ◽  
David C. Morrison
Keyword(s):  
Biologically Active ◽  
Clinical Isolates ◽  
Poor Correlation ◽  
Gram Negative Bacteria ◽  
Active Constituent ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Factor Alpha ◽  
Phenol Water ◽  
Necrosis Factor

ABSTRACT In general there is a poor correlation between serum lipopolysaccharide (LPS; the biologically active constituent of endotoxin) levels and mortality in septic patients. The objective of this study was to determine if chemical, structural, or biological differences among LPS from different clinical isolates of gram-negative bacteria might explain this discrepancy. LPS preparations were made using the hot phenol-water extraction method from eight clinical isolates of gram-negative bacteria. As a percentage of the total weight of the LPS, the phosphate content ranged from 3.0 to 13.8% (average, 6.7 ± 3.6%), and the 2-keto-3-deoxyoctonate content ranged from 1.9 to 27.4% (average, 8.9 ± 8.5%). These values were not dissimilar to those obtained for a reference endotoxin. In a standard measure of LPS activity, the Limulus amoebocyte lysate assay, there was approximately a twofold difference between the least and most active preparations. The two preparations with the greatest difference in their ability to elicit the secretion of tumor necrosis factor alpha from a mouse peritoneal macrophage cell line were similar in lethality when administered to mice sensitized to the effects of LPS by d(+)-galactosamine. These relatively minor differences in LPS activity seem unlikely to explain the generally observed discrepancy between serum endotoxin levels and mortality in patients with gram-negative sepsis.

scholarly journals Bacterial endotoxins: biological properties and mechanisms of action

1993 ◽  
Vol 2 (7) ◽  
pp. S11-S16 ◽  
Author(s):  
C. Galanos ◽  
M. A. Freudenberg
Keyword(s):  
Biological Properties ◽  
Mechanisms Of Action ◽  
Review Article ◽  
Gram Negative Bacteria ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Lethal Action ◽  
Bacterial Endotoxins ◽  
Factor Alpha ◽  
Necrosis Factor

Endotoxins (lipopolysaccharides, LPS) are agents of pathogenicity of Gram-negative bacteria, implicated in the development of Gram-negative shock. Endotoxin reacts with lipopolysaccharide-sensitive cells producing endogenous mediators such as tumour necrosis factor alpha (TNFα). Macrophages are cells mediating the toxic activities of LPS and TNFα is the primary mediator of the lethal action of endotoxin. This review article discusses the various mechanisms by which endotoxin hypersensitivity in bacteria-sensitized animals develops. The paper concludes with a discussion on the possible protective effect of carnitine congeners against the lethal action of LPS.

scholarly journals Comparative Effects of Ciprofloxacin and Ceftazidime on Cytokine Production in Patients with Severe Sepsis Caused by Gram-Negative Bacteria

2004 ◽  
Vol 48 (8) ◽  
pp. 2793-2798 ◽  
Author(s):  
C. A. Gogos ◽  
A. Skoutelis ◽  
A. Lekkou ◽  
E. Drosou ◽  
I. Starakis ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Group Versus ◽  
Gram Negative Bacteria ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

ABSTRACT In the present study the effect of ciprofloxacin versus ceftazidime on concentrations of pro- and anti-inflammatory cytokines in the sera of patients with severe sepsis was evaluated. The study included 58 previously healthy patients suffering from severe sepsis caused by gram-negative bacteria, treated with either ciprofloxacin or ceftazidime after thorough clinical and microbiological evaluation and followed up for clinical outcome. Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1b (IL-1b), IL-6, and IL-8 and of the anti-inflammatory cytokine IL-10, as well as of IL-1 receptor antagonist and soluble TNF receptors I and II, in serum were measured at baseline and 24 and 48 h after the first antimicrobial dose. Mean SAPS-II scores, development of septic shock, and mortality rates were similar in the two groups (43.2 ± 9.2, 21.4%, and 14.3% in the ceftazidime group versus 49.8 ± 11.3, 20%, and 13.3% in the ciprofloxacin group). Serum TNF-α and IL-6 levels at 24 and 48 h were significantly lower in the ciprofloxacin group, while the IL-10/TNF-α ratio was significantly higher, than those for the ceftazidime group. Among patients with high baseline TNF-α levels, there were significant increases in the IL-10/TNF-α ratio at both 24 and 48 h over that at admission for the ciprofloxacin group, while no differences were noted in the ceftazidime group. These results indicate that ciprofloxacin may have an immunomodulatory effect on septic patients by attenuating the proinflammatory response, while there is no evidence that differences in the cytokines measured have any impact on the final outcome.

scholarly journals Differential Tumor Necrosis Factor Alpha Expression and Release from Peritoneal Mouse Macrophages In Vitro in Response to Proliferating Gram-Positive versus Gram-Negative Bacteria

2000 ◽  
Vol 68 (8) ◽  
pp. 4422-4429 ◽  
Author(s):  
Wei Cui ◽  
David C. Morrison ◽  
Richard Silverstein
Keyword(s):  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
E Coli ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly different in vitro tumor necrosis factor alpha (TNF-α) responses when placed in coculture with peritoneal murine macrophages. These include quantitative differences in TNF-α mRNA expression and corresponding protein product secretion as well as kinetic differences in the profiles of the TNF-α responses. Further, lipopolysaccharide (from E. coli) is a major contributing factor to these differences, as revealed by comparative experiments with endotoxin-responsive (C3Heb/FeJ) and endotoxin-hyporesponsive (C3H/HeJ) macrophages. Nevertheless, the eventual overall magnitude of the TNF-α secretion of macrophages in response to S. aureus was at least equivalent to that observed with E. coli, while appearing at time periods hours later than the E. coli-elicited TNF-α response. Both the magnitude and kinetic profile of the TNF-α responses were found to be relatively independent of the rate of bacterial proliferation, at least to the extent that similar results were observed with both viable and paraformaldehyde-killed microbes. Nevertheless, S. aureus treated in culture with the carbapenem antibiotic imipenem manifests markedly altered profiles of TNF-α response, with the appearance of an early TNF-α peak not seen with viable organisms, a finding strikingly similar to that recently reported by our laboratory from in vivo studies (R. Silverstein, J. G. Wood, Q. Xue, M. Norimatsu, D. L. Horn, and D. C. Morrison, Infect. Immun. 68:2301–2308, 2000). In contrast, imipenem treatment of E. coli-cocultured macrophages does not significantly alter the observed TNF-α response either in vitro or in vivo. In conclusion, our data support the concept that the host inflammatory response of cultured mouse macrophages in response to viable gram-positive versus gram-negative microbes exhibits distinctive characteristics and that these distinctions are, under some conditions, altered on subsequent bacterial killing, depending on the mode of killing. Of potential importance, these distinctive in vitro TNF-α profiles faithfully reflect circulating levels of TNF-α in infected mice. These results suggest that coculture of peritoneal macrophages with viable versus antibiotic-killed bacteria and subsequent assessment of cytokine response (TNF-α) may be of value in clarifying, and ultimately controlling, related host inflammatory responses in septic patients.

scholarly journals Interaction of Antimicrobial Peptide Temporin L with Lipopolysaccharide In Vitro and in Experimental Rat Models of Septic Shock Caused by Gram-Negative Bacteria

2006 ◽  
Vol 50 (7) ◽  
pp. 2478-2486 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Federico Mocchegiani ◽  
Fiorenza Orlando ◽  
...  
Keyword(s):  
Septic Shock ◽  
Antimicrobial Peptide ◽  
Gram Negative Bacteria ◽  
Amphibian Skin ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Rat Models ◽  
E Coli ◽  
Tnf Α

ABSTRACT Sepsis remains a major cause of morbidity and mortality in hospitalized patients, despite intense efforts to improve survival. The primary lead for septic shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria. For these reasons, the quest for compounds with antiendotoxin properties is actively pursued. We investigated the efficacy of the amphibian skin antimicrobial peptide temporin L in binding Escherichia coli LPS in vitro and counteracting its effects in vivo. Temporin L strongly bound to purified E. coli LPS and lipid A in vitro, as proven by fluorescent displacement assay, and readily penetrated into E. coli LPS monolayers. Furthermore, the killing activity of temporin L against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide's affinity for endotoxin. Antimicrobial assays showed that temporin L interacted synergistically with the clinically used β-lactam antibiotics piperacillin and imipenem. Therefore, we characterized the activity of temporin L when combined with imipenem and piperacillin in the prevention of lethality in two rat models of septic shock, measuring bacterial growth in blood and intra-abdominal fluid, endotoxin and tumor necrosis factor alpha (TNF-α) concentrations in plasma, and lethality. With respect to controls and single-drug treatments, the simultaneous administration of temporin L and β-lactams produced the highest antimicrobial activities and the strongest reduction in plasma endotoxin and TNF-α levels, resulting in the highest survival rates.

scholarly journals Toxoplasma gondii Cyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner

2009 ◽  
Vol 77 (9) ◽  
pp. 3686-3695 ◽  
Author(s):  
Hany M. Ibrahim ◽  
Hiroshi Bannai ◽  
Xuenan Xuan ◽  
Yoshifumi Nishikawa
Keyword(s):  
Nitric Oxide ◽  
Toxoplasma Gondii ◽  
Inflammatory Responses ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Independent Manner ◽  
Necrosis Factor Alpha ◽  
Parasite Multiplication ◽  
Factor Alpha

ABSTRACT Toxoplasma gondii modulates pro- and anti-inflammatory responses to regulate parasite multiplication and host survival. Pressure from the immune response causes the conversion of tachyzoites into slowly dividing bradyzoites. The regulatory mechanisms involved in this switch are poorly understood. The aim of this study was to investigate the immunomodulatory role of T. gondii cyclophilin 18 (TgCyp18) in macrophages and the consequences of the cellular responses on the conversion machinery. Recombinant TgCyp18 induced the production of nitric oxide (NO), interleukin-12 (IL-12), and tumor necrosis factor alpha through its binding with cysteine-cysteine chemokine receptor 5 (CCR5) and the production of gamma interferon and IL-6 in a CCR5-independent manner. Interestingly, the treatment of macrophages with TgCyp18 resulted in the inhibition of parasite growth and an enhancement of the conversion into bradyzoites via NO in a CCR5-dependent manner. In conclusion, T. gondii possesses sophisticated mechanisms to manipulate host cell responses in a TgCyp18-mediated process.

scholarly journals Tumor necrosis factor alpha activates soluble guanylate cyclase in bovine glomerular mesangial cells via an L-arginine-dependent mechanism.

1990 ◽  
Vol 172 (6) ◽  
pp. 1843-1852 ◽  
Author(s):  
P A Marsden ◽  
B J Ballermann
Keyword(s):  
Guanylate Cyclase ◽  
Mesangial Cell ◽  
Soluble Guanylate Cyclase ◽  
Mesangial Cells ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Concentration Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Factor Alpha

Endothelium-derived nitric oxide (NO) causes vasodilatation by activating soluble guanylate cyclase, and glomerular mesangial cells respond to NO with elevations of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We explored whether mesangial cells can be stimulated to produce NO and whether NO modulates mesangial cell function in an autocrine or paracrine fashion. Tumor necrosis factor alpha (TNF-alpha) raised mesangial cell cGMP levels in a time- and concentration-dependent manner (threshold dose 1 ng/ml, IC50 13.8 ng/ml, maximal response 100 ng/ml). TNF-alpha-induced increases in mesangial cGMP content were evident at 8 h and maximal at 18-24 h. The TNF-alpha-induced stimulation of mesangial cell cGMP production was abrogated by actinomycin D or cycloheximide suggesting dependence on new RNA or protein synthesis. Hemoglobin and methylene blue, both known to inhibit NO action, dramatically reduced TNF-alpha-induced mesangial cell cGMP production. Superoxide dismutase, known to potentiate NO action, augmented the TNF-alpha-induced effect. Ng-monomethyl-L-arginine (L-NMMA) decreased cGMP levels in TNF-alpha-treated, but not vehicle-treated mesangial cells in a concentration-dependent manner (IC50 53 microM). L-arginine had no effect on cGMP levels in control or TNF-alpha-treated mesangial cells but reversed L-NMMA-induced inhibition. Interleukin 1 beta and lipopolysaccharide (LPS), but not interferon gamma, also increased mesangial cell cGMP content. Transforming growth factor beta 1 blunted the mesangial cell response to TNF-alpha. TNF-alpha-induced L-arginine-dependent increases in cGMP were also evident in bovine renal artery vascular smooth muscle cells, COS-1 cells, and 1502 human fibroblasts. These findings suggest that TNF-alpha induces expression in mesangial cell of an enzyme(s) involved in the formation of L-arginine-derived NO. Moreover, the data indicate that NO acts in an autocrine and paracrine fashion to activate mesangial cell soluble guanylate cyclase. Cytokine-induced formation of NO in mesangial and vascular smooth muscle cells may be implicated in the pathogenesis of septic shock.

scholarly journals High-Affinity Interaction between Gram-Negative Flagellin and a Cell Surface Polypeptide Results in Human Monocyte Activation

2000 ◽  
Vol 68 (10) ◽  
pp. 5525-5529 ◽  
Author(s):  
Patrick F. McDermott ◽  
Federica Ciacci-Woolwine ◽  
James A. Snipes ◽  
Steven B. Mizel
Keyword(s):  
Cell Surface ◽  
Mutational Analysis ◽  
Hypervariable Region ◽  
Gram Negative Bacteria ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Potent Inducer ◽  
Gram Negative ◽  
High Affinity ◽  
Tnf Α

ABSTRACT Flagella from diverse gram-negative bacteria induce tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) synthesis by human monocytes (F. Ciacci-Woolwine, P. F. McDermott, and S. B. Mizel, Infect. Immun. 67:5176–5185, 1999). In this study, we establish that purified flagellin (FliC or FljB), the major filament protein from Salmonella enterica serovar Enteritidis,S. enterica serovar Typhimurium, and Pseudomonas aeruginosa, is an extremely potent inducer of TNF-α production by human monocytes and THP-1 myelomonocytic cells. Fifty percent of maximal TNF-α production (EC50) was obtained with 1.5 × 10−11 M flagellin (0.75 ng/ml). Mutagenesis studies revealed that the central hypervariable region of flagellin is essential for the TNF-α-inducing activity of the protein. Although less active than the wild-type protein, a Salmonellaflagellin mutant composed of only the central hypervariable region retained substantial TNF-α-inducing activity at nanomolar concentrations. In contrast, the conserved amino- and carboxy-terminal regions are inactive. Mutational analysis of the hypervariable region revealed that it contains two equally active TNF-α-inducing domains. The ability of THP-1 cells to respond to purified flagellins is dramatically reduced by mild trypsin treatment of the cells. Taken together, our results demonstrate that the cytokine-inducing activity of flagellins from gram-negative bacteria results from the interaction of these proteins with high-affinity cell surface polypeptide receptors on monocytes.

scholarly journals The Host Antimicrobial Protein Calgranulin C Participates in the Control ofCampylobacter jejuniGrowth via Zinc Sequestration

2018 ◽  
Vol 86 (6) ◽  
Author(s):  
Janette M. Shank ◽  
Brittni R. Kelley ◽  
Joseph W. Jackson ◽  
Jessica L. Tweedie ◽  
Dana Franklin ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Poultry Meat ◽  
Antimicrobial Protein ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Full Resolution ◽  
Factor Alpha

ABSTRACTCampylobacter jejuniis a leading cause of bacterially derived gastroenteritis worldwide.Campylobacteris most commonly acquired through the consumption of undercooked poultry meat or through drinking contaminated water. Following ingestion,Campylobacteradheres to the intestinal epithelium and mucus layer, causing toxin-mediated inflammation and inhibition of fluid reabsorption. Currently, the human response to infection is relatively unknown, and animal hosts that model these responses are rare. As such, we examined patient fecal samples for the accumulation of the neutrophil protein calgranulin C during infection withCampylobacter jejuni. In response to infection, calgranulin C was significantly increased in the feces of humans. To determine whether calgranulin C accumulation occurs in an animal model, we examined disease in ferrets. Ferrets were effectively infected byC. jejuni, with peak fecal loads observed at day 3 postinfection and full resolution by day 12. Serum levels of interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α) significantly increased in response to infection, which resulted in leukocyte trafficking to the colon. As a result, calgranulin C increased in the feces of ferrets at the time whenC. jejuniloads decreased. Further, the addition of purified calgranulin C toC. jejunicultures was found to inhibit growth in a zinc-dependent manner. These results suggest that upon infection withC. jejuni, leukocytes trafficked to the intestine release calgranulin C as a mechanism for inhibitingC. jejunigrowth.

Angiography significantly decreased serum levels of IL-8 independent of artery stenosis

2020 ◽  
Author(s):  
Lida Zare ◽  
Akram Eidi ◽  
Mohammad Safarian ◽  
Mohammad Kazemi Arababadi
Keyword(s):  
Protective Factor ◽  
Serum Levels ◽  
Artery Stenosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Before And After ◽  
Elisa Technique ◽  
Factor Alpha

Abstract Background Angiography is a safe cardiovascular technique for the diagnosis and treatment of the cardiovascular disorders. The potential effects of angiography on the cytokines are yet to be clarified completely. Interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) are the important pro-inflammatory cytokines that participate in the pathogenesis of artery stenosis. The aim of his project was to study the angiography effects on the serum levels of IL-8 and TNF-α. Methods Fifty-five participants in three groups, without, with one and with more than one artery stenosis, were explored in this project. Serum levels of IL-8 and TNF-α were measured in the participants before and after angiography using enzyme linked immunosorbent assay (ELISA) technique. Results Serum levels of IL-8, but not TNF-α, were significantly decreased following angiography. X-ray doses had moderate positive correlation with serum levels of TNF-α in the patients with more than one artery stenosis. Serum levels of IL-8 and TNF-α were not different among male and female participants in all groups. Discussion Angiography may be a protective factor for inflammation in IL-8 dependent manner. Using angiography in the patients with more than one artery stenosis needs to be executed cautiously.

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