Monoclonal antibodies against alpha toxin of Clostridium perfringens

Sato, Hiroko; Chiba, Joe; Sato, Yuji

doi:10.1016/0378-1097(89)90480-1

Cited by 12 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The molecular basis of this difference in neutralizing ability is not clear. However, our observations coincide with those of other workers (19), who have reported the requirement of different stoichiometric ratios by any one antibody to inhibit, respectively, the PLC activity or in vivo effects of alpha-toxin.…”

supporting

confidence: 92%

Epitope mapping of the alpha-toxin of Clostridium perfringens

et al. 1991

View full text Add to dashboard Cite

A panel of monoclonal antibodies specific for the Clostridium perfringens alpha-toxin was produced by the fusion of X63.Ag8-653 cells with splenocytes from mice immunized either intrasplenically or intraperitoneally with an alpha-toxoid. The toxin-binding activity of each monoclonal antibody was evaluated. The monoclonal antibodies were also screened for their toxin-neutralizing potential in vitro, as determined by the inhibition of phospholipase C and hemolytic activities. In vivo inhibition of toxicity was assessed by the survival of mice challenged with preincubated alpha-toxin-antibody mixtures. Only one monoclonal antibody (3A4D10) was protective in vivo and neutralizing in both in vitro assays. Since 3A4D10 could inhibit both activities, the evidence suggests that these are colocated in the same area of the toxin molecule. This paper identifies a significant continuous linear binding region for 3A4D10 at positions 193 to 198 in the primary amino acid sequence of alpha-toxin.

show abstract

supporting

confidence: 92%

Epitope mapping of the alpha-toxin of Clostridium perfringens

et al. 1991

View full text Add to dashboard Cite

show abstract

“…This remains to be clarified. Other neutralizing MAbs (against perfringolysin 0 and SLO) which do not prevent binding of thiol-activated toxins but prevent lysis were isolated (16,22,27,28). To our knowledge, no MAb preventing binding of a thiol-activated toxin on the membrane has been isolated to date, and A4-8 is the first example of this type of antibody.…”

Section: Downloaded Frommentioning

confidence: 99%

Production and characterization of neutralizing and nonneutralizing monoclonal antibodies against listeriolysin O

et al. 1991

View full text Add to dashboard Cite

Listeriolysin O (LLO) is a thiol-activated toxin secreted by the facultative intracellular pathogen Listeria monocytogenes. LLO is essential for the survival of the bacterium in the infected cell because it promotes lysis of the phagosome membrane and escape of the bacterium into the cytosol. LLO was used as an antigen for the production of nine monoclonal antibodies (MAbs) in mice. Three of these could inhibit the hemolytic activity of LLO. One of them inhibited binding of LLO to erythrocyte membranes. The two other antibodies blocked the activity of LLO at a step subsequent to membrane binding. Only two of the nine MAbs recognized three other purified SH-activated toxins, streptolysin O, alveolysin, and pneumolysin. Western blot (immunoblot) analysis of culture supernatants of Listeria ivanovii and Listeria seeligeri, two hemolytic species of the genus Listeria, revealed that two MAbs recognized ivanolysin and seeligerolysin. The latter was also recognized by two other MAbs, including one of the neutralizing antibodies. MAbs raised against a peptide, ECTG LAWEWWR, present in all thiol-activated toxins sequenced to date, recognized all toxins and were not neutralizing. Taken together, these results demonstrate the existence of regions important for hemolytic activity that are unique to hemolysins of the genus Listeria and show that regions outside the conserved peptide are important for activity of LLO.

show abstract

“…The toxin-neutralizing antibodies used in this study were in the form of unconcentrated culture supernatant fluid from hybridomas that produce neutralizing monoclonal antibodies against v-toxin (clone 3H10, IgG1 [13]) and PLC (clone 1C6, IgG1 [14). Both hybridomas were gifts from Hiroko Sato (National Institutes of Health, Tokyo, Japan) and were cultured in RPMI plus L-glutamine and 10% fetal calf serum.…”

mentioning

confidence: 99%

Clostridial Gas Gangrene. II. Phospholipase C–Induced Activation of Platelet gpIIbIIIa Mediates Vascular Occlusion and Myonecrosis inClostridium perfringensGas Gangrene

Bryant¹,

et al. 2000

View full text Add to dashboard Cite

Clostridium perfringens gas gangrene is a fulminant infection, and radical amputation remains the single best treatment. It has been hypothesized that rapid tissue destruction is related to tissue hypoxia secondary to toxin-induced vascular obstruction, and previous studies demonstrated that phospholipase C (PLC) caused a rapid and irreversible decrease in skeletal muscle blood flow that paralleled the formation of intravascular aggregates of activated platelets, fibrin, and leukocytes. In this study, flow cytometry demonstrated that PLC stimulated platelet/neutrophil aggregation in a gpIIbIIIa-dependent fashion. Pretreatment of animals with heparin or depletion of leukocytes reduced blood-flow deficits, and aggregate formation caused by PLC. It is concluded that fulminant tissue destruction in gas gangrene results from profound attenuation of blood flow caused by PLC-induced, gpIIbIIIa-mediated formation of heterotypic platelet/polymorphonuclear leukocyte aggregates. Therapeutic strategies that target gpIIbIIIa may prevent vascular occlusion, maintain tissue viability, and provide an alternative to radical amputation for patients with this infection.

show abstract

Monoclonal antibodies against alpha toxin of Clostridium perfringens

Cited by 12 publications

References 12 publications

Epitope mapping of the alpha-toxin of Clostridium perfringens

Epitope mapping of the alpha-toxin of Clostridium perfringens

Production and characterization of neutralizing and nonneutralizing monoclonal antibodies against listeriolysin O

Clostridial Gas Gangrene. II. Phospholipase C–Induced Activation of Platelet gpIIbIIIa Mediates Vascular Occlusion and Myonecrosis inClostridium perfringensGas Gangrene

Contact Info

Product

Resources

About