Clostridium Difficile Toxin A Stimulates Intracellular Calcium Release and Chemotactic Response in Human Granulocytes

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1988 Jun 1

PMID 2838520

Citations 38

Authors

C Pothoulakis

R Sullivan

D A Melnick

G Triadafilopoulos

A S Gadenne

T Meshulam

J T Lamont

Affiliations

Soon will be listed here.

Abstract

Clostridium difficile, a common enteric pathogen, mediates tissue damage and intestinal fluid secretion by release of two protein exotoxins: toxin A, an enterotoxin, and toxin B, a cytotoxin. Because toxin A elicits an intense inflammatory reaction in vivo, we studied the effects of highly purified C. difficile toxins on activation of human granulocytes. Toxin A at concentrations of 10(-7) to 10(-6) M, but not toxin B, elicited a significant chemotactic and chemokinetic response by granulocytes that was comparable with that induced by the chemotactic factor N-FMLP (10(-7) M). Neither toxin stimulated release of superoxide anion from granulocytes. Toxin A produced a rapid, transient rise in cytosolic [Ca2+]i, as measured by quin 2 fluorescence. Pertussis toxin and depletion of intra- and extracellular calcium blocked the toxin A effect on cytosolic [Ca2+]i. These findings suggest that the inflammatory effects of C. difficile toxin A in the intestine may be related to its ability to mobilize intracellular Ca2+ and elicit a chemotactic response by granulocytes.

Citing Articles

Role of the Alteration in Calcium Homeostasis in Cell Death Induced by Toxin A and Toxin B.

Fettucciari K, Dini F, Marconi P, Bassotti G Biology (Basel). 2023; 12(8).

PMID: 37627001 PMC: 10452684. DOI: 10.3390/biology12081117.

Toxin CDT Induces Cytotoxic Responses in Human Mucosal-Associated Invariant T (MAIT) Cells.

Marquardt I, Jakob J, Scheibel J, Hofmann J, Klawonn F, Neumann-Schaal M Front Microbiol. 2022; 12:752549.

PMID: 34992584 PMC: 8727052. DOI: 10.3389/fmicb.2021.752549.

Mucins Dynamics in Physiological and Pathological Conditions.

Melhem H, Regan-Komito D, Hendrik Niess J Int J Mol Sci. 2021; 22(24).

PMID: 34948435 PMC: 8707880. DOI: 10.3390/ijms222413642.

Reactive Oxygen Species as Additional Determinants for Cytotoxicity of Clostridium difficile Toxins A and B.

Fradrich C, Beer L, Gerhard R Toxins (Basel). 2016; 8(1).

PMID: 26797634 PMC: 4728547. DOI: 10.3390/toxins8010025.

A Review of Clostridium difficile Infection at the University Hospital of the West Indies, Jamaica.

Clare-Pascoe N, Lee M, Murphy T, Nicholson A, Ferguson T West Indian Med J. 2015; 64(4):413-8.

PMID: 26624597 PMC: 4909078. DOI: 10.7727/wimj.2014.180.

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