PMID: 2500434Jul 5, 1989Paper

Internalization and processing of Bacillus anthracis lethal toxin by toxin-sensitive and -resistant cells

The Journal of Biological Chemistry
Y SinghA M Friedlander

Abstract

Anthrax lethal toxin consists of two separate proteins, protective antigen and lethal factor (LF). Certain macrophages and a mouse macrophage-like cell line, J774A.1, are lysed by low concentrations of lethal toxin. In contrast, another macrophage cell line, IC-21, and all other cell types tested were resistant to this toxin. To discover the basis for this difference, each step in the intoxication process was examined. No differences between sensitive and resistant cells were found in receptor binding or proteolytic activation of protective antigen, steps that are required prior to LF binding. To determine whether resistance results from a defect in translocation to the cytosol, we introduced LF into J774A.1 and IC-21 cells and a nonmacrophage cell line (L6 myoblast) by osmotic lysis of pinocytic vesicles. Only J774A.1 cells were lysed; no effect was observed in IC-21 and L6 cells. These results suggest that resistant cells either lack the intracellular target of LF or fail to process LF to an active form. The relatively low potency of LF introduced into J774A.1 cells by osmotic lysis suggests that protective antigen may also be required at a stage subsequent to endocytosis.

Related Concepts

Related Feeds

Anthrax Vaccines

Three different types of anthrax vaccines are available; a live-attenuated, an alum-precipitated cell-free filtrate and a protein recombinant vaccine. The effectiveness between the three is uncertain, but the live-attenuated have shown to reduce the risk of anthrax with low adverse events. Here is the latest research on anthrax vaccines.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Anthrax Vaccines (ASM)

Three different types of anthrax vaccines are available; a live-attenuated, an alum-precipitated cell-free filtrate and a protein recombinant vaccine. The effectiveness between the three is uncertain, but the live-attenuated have shown to reduce the risk of anthrax with low adverse events. Here is the latest research on anthrax vaccines.

Anthrax

Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Here is the latest research on Anthrax.