Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides

Morrison, David C.; Jacobs, Diane M.

doi:10.1016/0019-2791(76)90181-6

Cited by 750 publications

(460 citation statements)

References 16 publications

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“…3, and 76 * 4 pg protein/well, respectively; n = 4 for a 96-well culture). Polymyxin B (10 pg/ml), which inactivates lipopolysaccharide (24), was generally incubated for 30 minutes at 37°C with TNF (or the cytqkine tested) prior to addition to the culture at a final concentration of 1 pg/ml.…”

Section: Methodsmentioning

confidence: 99%

Effects of tumor necrosis factor α and β on resorption of human articular cartilage and production of plasminogen activator by human articular chondrocytes

Campbell

Piccoli

Roberts

et al. 1990

Arthritis & Rheumatism

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We examined the effects of recombinant human tumor necrosis factor (TNF) on human articular cartilage and chondrocytes in culture. Both TNFa and TNFP stimulated cartilage matrix breakdown during prolonged culture and elevated the levels of plasminogen activator (PA) activity in both the supernatants and cell layers of cultured chondrocytes. Characterization of the PA activities by immunochemistry and by zymography following gel electrophoresis indicated that human chondrocytes produce both urokinase-type PA and tissuetype PA in response to TNF. The addition of both interleukin-1 and TNFa or TNFP to chondrocyte cultures demonstrated a synergism between these cytokines in the generation of PA activity in the culture supernatants and cell layers. Our results suggest that both activated lymphocytes and monocytes may contribute to the cartilage destruction of inflammatory arthritis through their stimulation of chondrocytes with TNFP and TNFa, respectively. Since PA is the only neutral proteinase reported to be elevated in TNF-stimulated chondrocyte cultures, it could have an important role in TNF-mediated cartilage destruction.

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Section: Methodsmentioning

confidence: 99%

Effects of tumor necrosis factor α and β on resorption of human articular cartilage and production of plasminogen activator by human articular chondrocytes

Campbell

Piccoli

Roberts

et al. 1990

Arthritis & Rheumatism

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“…Neutralization of endotoxin in CSR We examined the neutralization of endotoxin in CSF by polymyxin B, which binds nonspecifically to the lipid A moiety of endotoxin [17], and by a monoclonal antibody directed against lipid A. Starting 16 hr after infection, polymyxin B was infused for 3 hr at a dosage of 5,000 U/kg per hr, either simultaneously with antibiotic treatment (cefotaxime) or alone.…”

Section: Methodsmentioning

confidence: 99%

Antibiotic Therapy, Endotoxin Concentration in Cerebrospinal Fluid, and Brain Edema in Experimental Escherichia coli Meningitis in Rabbits

Täuber¹,

Shibl²,

Hackbarth³

et al. 1987

Journal of Infectious Diseases

161

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We investigated the effect of cefotaxime and chloramphenicol on endotoxin concentrations in cerebrospinal fluid (CSF) and on the development of brain edema in rabbits with Escherichia coli meningitis. Both antibiotics were similarly effective in reducing bacterial titers. Cefotaxime, but not chloramphenicol, induced a marked increase of endotoxin in CSF, from log., 1.5 ± 0.8 to log., 2.8 ± 0.7 ng/ml (P < .01). This result was associated with an increase in brain water content (405 ± 12 g of water/loo g of dry weight compared with 389 ± 8 g in untreated controls; P < .01), whereas in animals treated with chloramphenicol, brain water content was identical to controls. The cefotaxime-induced increase in endotoxin concentration and brain edema were both neutralized by polymyxin B, which binds to the lipid A moiety of endotoxin, or by a monoclonal antibody to lipid A. These results indicate that treating gram-negative bacillary meningitis with selected antibiotics induces increased endotoxin concentrations in CSF that are associated with brain edema.

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“…Some cationic peptides, including the antibiotic polymyxin B, have been shown to bind to the lipid A region of LPS and block the LAL endotoxic and immunobiological activities of LPS [28,29]. To examine whether Tm-Gp also inhibits LPS activity, we assessed the clotting activities of LAL by LPS or compound 506 in the presence of Tm-Gp.…”

Section: Effect Of Tm-gp On Limulus Amoebocyte Lysate (Lal) Activitiesmentioning

confidence: 99%

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

2003

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Spirochetes are well-known as causative agents of various chronic infectious diseases. Glycolipids of small-sized Treponema spirochetes have been shown to exhibit immunostimulating activities. In this study, we found that a glycoconjugate preparation obtained from Treponema medium (Tm-Gp), an intermediate-sized oral Treponema seen in subgingival plaque from patients with chronic periodontal diseases, diminished the LPS-induced activation of a human monocytic cell line, while TNF- § -induced activation was unaffected. NF-‹ B activation in Ba/F3 cells expressing murine Toll-like receptor (TLR) 4 and MD-2 was inhibited by Tm-Gp in a CD14/LPS-binding protein (LBP)-dependent manner when stimulated with LPS or its active center lipid A but not when stimulated with Taxol. Tm-Gp blocked the binding of LPS to immobilized CD14 and LBP and inhibited nitric oxide (NO) production by a murine M ¤ cell line following stimulation with peptidoglycan and LPS in the presence of FBS, while NO production in response poly (I:C) RNA or CpG DNA remained unaffected. The inhibitory effects of Tm-Gp seem to be attributable to the lipophilic portion of the glycoconjugate. These results indicate that T. medium contains a glycoconjugate possessing an inhibitory effect on TLR-mediated cell activation through interaction with LBP and CD14.

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Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides

Cited by 750 publications

References 16 publications

Effects of tumor necrosis factor α and β on resorption of human articular cartilage and production of plasminogen activator by human articular chondrocytes

Effects of tumor necrosis factor α and β on resorption of human articular cartilage and production of plasminogen activator by human articular chondrocytes

Antibiotic Therapy, Endotoxin Concentration in Cerebrospinal Fluid, and Brain Edema in Experimental Escherichia coli Meningitis in Rabbits

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

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