Clostridium difficile toxin A stimulates intracellular calcium release and chemotactic response in human granulocytes. (original) (raw)

Research Article Free access | 10.1172/JCI113514

R Sullivan, D A Melnick, G Triadafilopoulos, A S Gadenne, T Meshulam, and J T LaMont

Section of Gastroenterology, Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.

Find articles by Pothoulakis, C. in:PubMed |Google Scholar

Section of Gastroenterology, Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.

Find articles by Sullivan, R. in:PubMed |Google Scholar

Section of Gastroenterology, Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.

Find articles by Melnick, D. in:PubMed |Google Scholar

Section of Gastroenterology, Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.

Find articles by Triadafilopoulos, G. in:PubMed |Google Scholar

Section of Gastroenterology, Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.

Find articles by Gadenne, A. in:PubMed |Google Scholar

Section of Gastroenterology, Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.

Find articles by Meshulam, T. in:PubMed |Google Scholar

Section of Gastroenterology, Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.

Find articles by LaMont, J. in:PubMed |Google Scholar

Published June 1, 1988 -More info

Published June 1, 1988 -Version history

View PDF

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.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history