Reduction of endotoxin-induced vascular permeability by monoclonal antibodies against lipopolysaccharide determinants

R. M. Rubin, J. Noland, James (Jim) Rosenbaum

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Endotoxin, a bacterial lipopolysaccharide implicated in the pathogenesis of septic shock, markedly alters vascular permeability following intravenous injection in rabbits. We investigated the ability of murine monoclonal antibodies to confer protection against endotoxin-induced increases in a rabbit model of ocular vascular permeability. Four monoclonal antibodies of differing specificities as well as polymyxin B were compared for their effects on endotoxin from either Eschericia coli or Pseudomonas aeruginosa. Preincubation of endotoxin with antibodies directed against Pseudomonas O side chain or core glycolipid resulted in marked attenuation of vascular permeability due to Pseudomonas endotoxin, but not E. coli endotoxin. Antilipid A antibodies were not significantly effective in neutralizing either endotoxin with in vitro preincubation. Low avidity of the antilipid A antibody, low density of lipid A binding sites, or inaccessibility of the lipid A may have prevented more marked interactions. When administered intravenously prior to endotoxin challenge, none of the antibodies demonstrated the ability to provide specific protection to subsequent endotoxin in this model. They did provide partial nonspecific protection against endotoxins regardless of epitope specificity. When administered prophylactically, polymyxin B, an antibiotic that binds to lipid A, was highly effective in neutralizing the toxic effects of endotoxin. Since antibodies to lipid A reduce mortality in septic shock, the failure to demonstrate efficacy in this study may be due to the marked sensitivity of the rabbit eye to endotoxin. Alternatively, beneficial effects from antiendotoxin antibodies in septic shock may be unrelated to the inhibition of vascular permeability. Some protection from antiendotoxin antibodies may be due to enhancement of nonspecific mechanisms.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalCirculatory Shock
Volume36
Issue number3
StatePublished - 1992

Fingerprint

Capillary Permeability
Endotoxins
Lipopolysaccharides
Monoclonal Antibodies
Lipid A
Septic Shock
Antibodies
Polymyxin B
Rabbits
Pseudomonas
Antibody Specificity
Poisons
Glycolipids
Intravenous Injections
Pseudomonas aeruginosa
Epitopes
Binding Sites
Escherichia coli
Anti-Bacterial Agents

Keywords

  • endotoxin
  • lipid A
  • LPS
  • polymyxin B
  • septic shock

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Reduction of endotoxin-induced vascular permeability by monoclonal antibodies against lipopolysaccharide determinants. / Rubin, R. M.; Noland, J.; Rosenbaum, James (Jim).

In: Circulatory Shock, Vol. 36, No. 3, 1992, p. 217-223.

Research output: Contribution to journalArticle

@article{e81f07580f8b4edca79986b654dc1a84,
title = "Reduction of endotoxin-induced vascular permeability by monoclonal antibodies against lipopolysaccharide determinants",
abstract = "Endotoxin, a bacterial lipopolysaccharide implicated in the pathogenesis of septic shock, markedly alters vascular permeability following intravenous injection in rabbits. We investigated the ability of murine monoclonal antibodies to confer protection against endotoxin-induced increases in a rabbit model of ocular vascular permeability. Four monoclonal antibodies of differing specificities as well as polymyxin B were compared for their effects on endotoxin from either Eschericia coli or Pseudomonas aeruginosa. Preincubation of endotoxin with antibodies directed against Pseudomonas O side chain or core glycolipid resulted in marked attenuation of vascular permeability due to Pseudomonas endotoxin, but not E. coli endotoxin. Antilipid A antibodies were not significantly effective in neutralizing either endotoxin with in vitro preincubation. Low avidity of the antilipid A antibody, low density of lipid A binding sites, or inaccessibility of the lipid A may have prevented more marked interactions. When administered intravenously prior to endotoxin challenge, none of the antibodies demonstrated the ability to provide specific protection to subsequent endotoxin in this model. They did provide partial nonspecific protection against endotoxins regardless of epitope specificity. When administered prophylactically, polymyxin B, an antibiotic that binds to lipid A, was highly effective in neutralizing the toxic effects of endotoxin. Since antibodies to lipid A reduce mortality in septic shock, the failure to demonstrate efficacy in this study may be due to the marked sensitivity of the rabbit eye to endotoxin. Alternatively, beneficial effects from antiendotoxin antibodies in septic shock may be unrelated to the inhibition of vascular permeability. Some protection from antiendotoxin antibodies may be due to enhancement of nonspecific mechanisms.",
keywords = "endotoxin, lipid A, LPS, polymyxin B, septic shock",
author = "Rubin, {R. M.} and J. Noland and Rosenbaum, {James (Jim)}",
year = "1992",
language = "English (US)",
volume = "36",
pages = "217--223",
journal = "Journal of inflammation",
issn = "1078-7852",
publisher = "Springer Nature",
number = "3",

}

TY - JOUR

T1 - Reduction of endotoxin-induced vascular permeability by monoclonal antibodies against lipopolysaccharide determinants

AU - Rubin, R. M.

AU - Noland, J.

AU - Rosenbaum, James (Jim)

PY - 1992

Y1 - 1992

N2 - Endotoxin, a bacterial lipopolysaccharide implicated in the pathogenesis of septic shock, markedly alters vascular permeability following intravenous injection in rabbits. We investigated the ability of murine monoclonal antibodies to confer protection against endotoxin-induced increases in a rabbit model of ocular vascular permeability. Four monoclonal antibodies of differing specificities as well as polymyxin B were compared for their effects on endotoxin from either Eschericia coli or Pseudomonas aeruginosa. Preincubation of endotoxin with antibodies directed against Pseudomonas O side chain or core glycolipid resulted in marked attenuation of vascular permeability due to Pseudomonas endotoxin, but not E. coli endotoxin. Antilipid A antibodies were not significantly effective in neutralizing either endotoxin with in vitro preincubation. Low avidity of the antilipid A antibody, low density of lipid A binding sites, or inaccessibility of the lipid A may have prevented more marked interactions. When administered intravenously prior to endotoxin challenge, none of the antibodies demonstrated the ability to provide specific protection to subsequent endotoxin in this model. They did provide partial nonspecific protection against endotoxins regardless of epitope specificity. When administered prophylactically, polymyxin B, an antibiotic that binds to lipid A, was highly effective in neutralizing the toxic effects of endotoxin. Since antibodies to lipid A reduce mortality in septic shock, the failure to demonstrate efficacy in this study may be due to the marked sensitivity of the rabbit eye to endotoxin. Alternatively, beneficial effects from antiendotoxin antibodies in septic shock may be unrelated to the inhibition of vascular permeability. Some protection from antiendotoxin antibodies may be due to enhancement of nonspecific mechanisms.

AB - Endotoxin, a bacterial lipopolysaccharide implicated in the pathogenesis of septic shock, markedly alters vascular permeability following intravenous injection in rabbits. We investigated the ability of murine monoclonal antibodies to confer protection against endotoxin-induced increases in a rabbit model of ocular vascular permeability. Four monoclonal antibodies of differing specificities as well as polymyxin B were compared for their effects on endotoxin from either Eschericia coli or Pseudomonas aeruginosa. Preincubation of endotoxin with antibodies directed against Pseudomonas O side chain or core glycolipid resulted in marked attenuation of vascular permeability due to Pseudomonas endotoxin, but not E. coli endotoxin. Antilipid A antibodies were not significantly effective in neutralizing either endotoxin with in vitro preincubation. Low avidity of the antilipid A antibody, low density of lipid A binding sites, or inaccessibility of the lipid A may have prevented more marked interactions. When administered intravenously prior to endotoxin challenge, none of the antibodies demonstrated the ability to provide specific protection to subsequent endotoxin in this model. They did provide partial nonspecific protection against endotoxins regardless of epitope specificity. When administered prophylactically, polymyxin B, an antibiotic that binds to lipid A, was highly effective in neutralizing the toxic effects of endotoxin. Since antibodies to lipid A reduce mortality in septic shock, the failure to demonstrate efficacy in this study may be due to the marked sensitivity of the rabbit eye to endotoxin. Alternatively, beneficial effects from antiendotoxin antibodies in septic shock may be unrelated to the inhibition of vascular permeability. Some protection from antiendotoxin antibodies may be due to enhancement of nonspecific mechanisms.

KW - endotoxin

KW - lipid A

KW - LPS

KW - polymyxin B

KW - septic shock

UR - http://www.scopus.com/inward/record.url?scp=0026534754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026534754&partnerID=8YFLogxK

M3 - Article

C2 - 1377103

AN - SCOPUS:0026534754

VL - 36

SP - 217

EP - 223

JO - Journal of inflammation

JF - Journal of inflammation

SN - 1078-7852

IS - 3

ER -