The Interaction of Pseudomonas Toxins with Epithelial Cell Membranes: A Primary Stage in the Pathogenesis Sequence of Cellular Intoxication
Abstract
The purpose of this work has been to determine the nature of alterations of the cell membrane which result from its interaction with an penetration by Pseudomonas exotoxin (PE) or endotoxin or Diphtheria toxin (DE); and to determine what relation, if any, exists between the enzymatic function (ADPRase) in the a-fragment of the PE peptide and its ability to gain entry into a host cell. The turtle bladder was chosen as the host cell system because its major function, the reaborption of Na, C1, and HC03, depends on readily-measured electrical parameters, e.g. the transepithelial potential (PD), conductance (G or 1/R), and short-circuiting current (Isc). The main findings to this data are: (i) When added to the mucosal fluid but not to the serosal fluid, the proenzymatic form of PE (i.e. that with low ADPRase activity) and not the enzymatically-activated form decreases the Isc, PD, and G of bladders in Na-rich and Na-free media. (ii) Pre-mixing of PE with a 2:1 molar excess of anti-PE antibodies effectively blocks the effect of this exotoxin on the bladder; as does pre-heating (100 C) of the exotoxin. (iii) In contrast to the inhibitory action of PE, the diphtherial exotoxin (DE) increases the Isc and G after its addition to either the mucosal or serosal fluid in a Na-rich system, but only after addition to the mucosal fluid in a Na-free system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1978
- Accession Number
- ADA130569
Entities
People
- William A. Brodsky
Organizations
- Icahn School of Medicine at Mount Sinai