Tetanus Toxin

Heyningen, W. E. van; Mellanby, Jane

doi:10.1016/b978-0-12-046502-6.50008-3

Cited by 26 publications

(13 citation statements)

References 84 publications

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“…oedematiens type A &toxin. Because cholesterol inhibits these lysins in a manner identical to that for streptolysin 0 (van Heyningen, 1950), this finding provides additional evidence that cholesterol is involved. However, lysis by saponin which is also inhibited by free cholesterol (Ponder, 1945), was not affected by inhibitory factor (table The results in table I11 suggest that if cholesterol is involved it is not released from lipoprotein as free cholesterol molecules.…”

Section: Production Of Inhibitory Factorsupporting

confidence: 49%

Partial Characterisation of an Inhibitor of Streptolysin O Produced by Bacterialgrowth in Serum

Watson

Kerr

1975

Journal of Medical Microbiology

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THE antistreptolysin 0 test is a reliable indicator of streptococcal infection. Non-specific inhibition of streptolysin 0 is uncommon but has been described in viral hepatitis and in jaundice. Free cholesterol inhibits streptolysin 0 in low concentration (Hewitt and Todd, 1939), but cholesterol in normal serum is not inhibitory (Watson, Rose and Kerr, 1972). However, we have encountered occasional false positive antistreptolysin tests where the sera have been contaminated with bacteria. Nevertheless, it must be stressed that such contamination is an uncommon cause of confusion in the standard antistreptolysin test. The mechanism of bacterial action on streptolysin 0 has not been investigated in detail. Hewitt and Todd (1939) found certain unspecified bacteria to produce an effect and suggested that cholesterol might be involved in some way in sera contaminated with a strain of Bacillus subtilis.Previously we showed that the inhibitor is produced only in cultures containing serum and that filtrates of broth cultures had no inhibitory activity (Watson and Kerr, 1973a). Inhibitory activity developed slowly in cultures containing serum-broth mixtures, being maximal after 4-7 days at 37OC. Most strains of Pseudomonas aeruginosa and Staphylococcus auras produced the inhibitory factor. Initial ultrafiltration studies with highly active sera contaminated with positive strains did not suggest that bacteria released free cholesterol from lipoproteins. The mechanism has now been studied in more detail. MATERIALS AND METHODSBacterial cultures. The majority of strains investigated were isolated from culture plates obtained from routine laboratory specimens. In addition, some 50 strains of Ps. aeruginosa kept in stock culture for several years comprising isolates from pathological specimens and

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Section: Production Of Inhibitory Factorsupporting

confidence: 49%

Partial Characterisation of an Inhibitor of Streptolysin O Produced by Bacterialgrowth in Serum

Watson

Kerr

1975

Journal of Medical Microbiology

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“…The toxigenic light chain (50 kDa) remains linked by a single disulfide bond to the binding domain of the targeting heavy chain (100 kDa). The principal targets of TeTx are both the central and peripheral nervous systems where inhibition of neurotransmitter release has been demonstrated (for review, see Mellanby, 1984;van Heyningen, 1986;Wellhöner, 1992;Niemann et al, 1994).…”

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confidence: 99%

Tetanus Toxin Enhances Protein Kinase C Activity Translocation and Increases Polyphosphoinositide Hydrolysis in Rat Cerebral Cortex Preparations

Gil

Ruiz‐Meana

Álava

et al. 1998

Journal of Neurochemistry

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Abstract:Tetanus toxin (TeTx) has been recently demonstrated to be a Zn 2~-dependentendopeptidase that cleaves synaptobrevin, a protein in part responsible for neurotransmitter release. Nevertheless, certain aspects of TeTx action, for example, the causal relationship between TeTx and protein kinase C (PKC; EC 2.7.1.37) activity cannot be explained by this cleavage alone. In the present study, primary neurons from fetal rat brain, synaptosomes, and whole slices have been used to examine this issue. Low doses of TeTx ( 10_8 M) caused PKC activity translocation in a manner similar to that produced by 1 2-O-tetradecanoylphorbol 13-acetate (TPA). TPA ( 10M) caused sustained PKC activity translocation, whereas TeTx produced translocation followed by relocation, depending on the dose and time of exposure. Immunoidentification with a monoclonal antibody recognizing both a and /3 isoforms revealed that TeTx induced moderate losses of PKC in the cytosolic fraction, without a comparable increase in the particulate fraction. Although moderate losses of activity were also noticed in the cytosolic fraction, the inconsistency with respect to activity translocation may be explained by translocation of additional PKC isoforms that are not identified by the antibody. Comparable levels of water-soluble inositol phosphate-labeled intermediates were obtained after treatment of cerebral cells and/or cortical brain slices with TeTx. Significant increases of 19 and 114% in the watersoluble myo-[2-3H]inositol-labeled inositol phosphate metabolites were found in cerebral cell culture and brain slices, respectively, after treatment with 10~8M TeTx. TeTx (10_8 M) increased to the same degree the watersoluble inositol phosphate levels as did serotonin (10-M ) or carbachol (10-6 M). lt is suggested that part of the signaling cascade of TeTx consists of a component involving inositol phospholipid hydrolysis, which is associated with PKC activity translocation. Key Words: Tetanus toxin-Protein kinase C-Phorbol ester-Neuronal cultures-Polyphosphoinositide hydrolysis-Phospholipase C-Synaptosomes.

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“…There have been many studies on the production of human anti-tetanus MAbs (2,4,5,6,7,8,12,13,14,15,17,24,26,28,29) for two reasons. First, these MAbs would be useful clinically in place of horse antitoxin, which is not safe, or human polyclonal antibody, which is available in only limited amounts.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of toxin-neutralization by anti-tetanus human monoclonal antibodies directed against the three functional domains [A], [B], and [C] of the tetanus toxin molecule and a reliable method for evaluating the protective effects of monoclonal antibodies

et al. 1992

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Five anti-tetanus human monoclonal antibodies (MAbs) produced by hybrid cell lines we established previously were characterized. Their abilities to neutralize tetanus toxin in vitro and to protect mice against challenge with toxin were studied by observing the changes in the progress of symptoms in mice. Immunostaining showed that MAbs MAb-G4 and G2 recognized the N-terminal domain, [A] and the C-terminal domain, [C] of the tetanus toxin molecule, respectively, while MAbs MAb-G1, G3 and G6 recognized its middle domain, [B]. Enzyme-linked immunosorbent assay showed that the binding affinity of MAb-G3 was 2.9 x 10(10) M-1 and those of the other MAbs were as high as approximately 10(11) M-1. In in vitro neutralization experiments, at sufficient doses all the MAbs as single reagents protected mice completely against the effect of tetanus toxin. However, at lower doses than those sufficient to rescue mice, the kinetic patterns of progress of symptoms with the individual MAbs differed with each other and, except for MAb-G4, were different from that of anti-tetanus human polyclonal antibody. They suppressed the development and/or slowed the rate of progress of symptoms for over 96 h and delayed death of the mice. We propose that the comparison of the minimum survival dose with that of human polyclonal antibody of known international units is a reliable method for estimating the actual protective activity of a MAb. Intravenous (IV) injection of doses of individual MAbs or their mixtures at over 0.03 IU per mouse protected mice from subsequent challenge with 20 MLD of tetanus toxin.(ABSTRACT TRUNCATED AT 250 WORDS)

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Tetanus Toxin

Cited by 26 publications

References 84 publications

Partial Characterisation of an Inhibitor of Streptolysin O Produced by Bacterialgrowth in Serum

Partial Characterisation of an Inhibitor of Streptolysin O Produced by Bacterialgrowth in Serum

Tetanus Toxin Enhances Protein Kinase C Activity Translocation and Increases Polyphosphoinositide Hydrolysis in Rat Cerebral Cortex Preparations

Characteristics of toxin-neutralization by anti-tetanus human monoclonal antibodies directed against the three functional domains [A], [B], and [C] of the tetanus toxin molecule and a reliable method for evaluating the protective effects of monoclonal antibodies

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