Differential induction of tumor necrosis factor by bacteria expressing rough and smooth lipopolysaccharide phenotypes

Kelly, N. M.; Young, Lynnette D.; Cross, Alan S.

doi:10.1128/iai.59.12.4491-4496.1991

Cited by 41 publications

(25 citation statements)

References 20 publications

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“…This may occur by natural blebbing of outer membrane fragments during growth of the organism (23). Alternatively, some studies suggest that naturally rough organisms shed significantly more LPS than smooth chemotypes during growth and therefore may be superior inducers of tumor necrosis factor (TNF) during gram-negative sepsis (17). Other mechanisms which could expose rough LPS would be the natural death of the bacteria; the action of host defense systems, including complement-mediated lysis (42,43) and opsonization by macrophages with subsequent release of bacterial cell wall components (6,7); and antibiotics which alter the structural integrity of the bacterial membrane (10,26,43).…”

Section: Discussionmentioning

confidence: 99%

Reactivity of the human antiendotoxin immunoglobulin M monoclonal antibody HA-1A with lipopolysaccharides from rough and smooth gram-negative organisms

Mascelli¹,

Frederick²,

Ely³

et al. 1993

Infect Immun

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Clinical data suggest that the human immunoglobulin M antiendotoxin antibody HA-1A reduced mortality in patients diagnosed with gram-negative bacteremia and bacteremia with shock. Previous studies have demonstrated that HA-1A binds to the lipid A domain of lipopolysaccharide (LPS). The present study evaluated the ability of HA-1A to interact with LPSs isolated from various strains of gram-negative bacteria by using liquid-phase rate nephelometry and solid-phase immunoblotting assays. HA-1A formed immune complexes in solution with LPSs isolated from both rough and smooth gram-negative organisms. Western blot (immunoblot) analysis of these LPS preparations revealed that HA-1A bound to LPS isolated from rough gram-negative organisms and to a rough LPS-like component present in smooth LPS. HA-1A also bound to LPS-protein complexes found in certain commercial rough LPS preparations. Preincubation of HA-1A with lipid A completely blocked subsequent binding of HA-1A to LPS in both liquid-and solid-phase assay formats, suggesting that the interaction of HA-lA with LPS is through the lipid A domain. Evidence that the binding of HA-lA to LPS was mediated through the antigen-combining (Fv) region of the antibody was provided by the finding that a murine anti-idiotypic antibody to HA-1A inhibited binding. These findings suggested that the broad antiendotoxin reactivity exhibited by HA-1A appeared to be due to the ability of HA-1A to bind to the conserved lipid A moiety of LPSs derived from both smooth-and rough-phenotype gram,-negative bacterial strains.

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Section: Discussionmentioning

confidence: 99%

Reactivity of the human antiendotoxin immunoglobulin M monoclonal antibody HA-1A with lipopolysaccharides from rough and smooth gram-negative organisms

Mascelli¹,

Frederick²,

Ely³

et al. 1993

Infect Immun

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“…The murine macrophage cell line RAW 264.7 was obtained from the American Type Culture Collection (Manassas, Va.). The cells were maintained in Dulbecco's modified Eagle medium supplemented with 10% fetal calf serum and passaged as described previously (13). For stimulation with bacterial products, the cells were plated at a density of 10 6 /well in 24-well plates, incubated overnight to permit adherence, and then washed with fresh medium before stimulation.…”

Section: Methodsmentioning

confidence: 99%

Interaction of Cationic Peptides with Lipoteichoic Acid and Gram-Positive Bacteria

1999

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Compounds with antiendotoxin properties have been extensively studied for their potential as therapeutic agents for sepsis attributable to gram-negative bacteria. However, with the increasing incidence of gram-positive sepsis, there is interest in identifying compounds with a broad spectrum of action against both gram-positive and gram-negative bacteria. A series of synthetic α-helical cationic peptides related to bee melittin and silk moth cecropin have previously been shown to bind lipopolysaccharide (LPS) with high affinity, inhibit LPS-induced tumor necrosis factor alpha (TNF-α) production in vitro and in vivo, and kill gram-negative bacteria. In this study, we analyzed whether these peptides were active against gram-positive bacteria; whether they could bind to lipoteichoic acid (LTA), the major proinflammatory structure on gram-positive bacteria; and whether they could block the ability of LTA to promote the release of cytokines by the RAW 264.7 murine macrophage cell line. We found that the cationic peptides demonstrated moderate growth-inhibitory activity toward gram-positive bacteria. In addition, the peptides bound LTA with high affinity. This correlated with the ability of the peptides to block LTA-induced production of TNF and interleukin-6 by RAW 264.7 cells but did not correlate with their ability to kill the bacteria. The peptides also effectively inhibited LTA-induced TNF production in a whole human blood assay. The peptides were also able to partly block the ability of heat-killed Staphylococcus aureus, as well as soluble products of live S. aureus, to stimulate cytokine production by macrophages. Our results indicate that these cationic peptides may be useful to prevent sepsis and inflammation caused by both gram-negative and gram-positive bacteria.

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“…Blockage of TNF and IL-6 induction in RAW macrophage cells by smooth LPS. The murine cell line RAW 264.7 was obtained from the American Type Culture Collection, Manassas, Va., and maintained and passaged as described previously (12). TNF and IL-6 induction experiments with LPS were performed for 6 h as described by Kelly et al (12), using LPS at a final concentration of 100 ng/ml.…”

mentioning

confidence: 99%

Biological Properties of Structurally Related α-Helical Cationic Antimicrobial Peptides

1999

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A series of α-helical cationic antimicrobial peptide variants with small amino acid changes was designed. Alterations in the charge, hydrophobicity, or length of the variant peptides did not improve the antimicrobial activity, and there was no statistically significant correlation between any of these factors and the MIC forPseudomonas aeruginosa, Escherichia coli, orSalmonella typhimurium. Individual peptides demonstrated synergy with conventional antibiotics against antibiotic-resistant strains of P. aeruginosa. The peptides varied considerably in the ability to bind E. coli O111:B4 lipopolysaccharide (LPS), and this correlated significantly with their antimicrobial activity and ability to block LPS-stimulated tumor necrosis factor and interleukin-6 production. In general, the peptides studied here demonstrated a broad range of activities, including antimicrobial, antiendotoxin, and enhancer activities.

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Differential induction of tumor necrosis factor by bacteria expressing rough and smooth lipopolysaccharide phenotypes

Cited by 41 publications

References 20 publications

Reactivity of the human antiendotoxin immunoglobulin M monoclonal antibody HA-1A with lipopolysaccharides from rough and smooth gram-negative organisms

Reactivity of the human antiendotoxin immunoglobulin M monoclonal antibody HA-1A with lipopolysaccharides from rough and smooth gram-negative organisms

Interaction of Cationic Peptides with Lipoteichoic Acid and Gram-Positive Bacteria

Biological Properties of Structurally Related α-Helical Cationic Antimicrobial Peptides

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