Advertisement

Research Article Free access | 10.1172/JCI117080

Neutrophil recruitment in Clostridium difficile toxin A enteritis in the rabbit.

C P Kelly, S Becker, J K Linevsky, M A Joshi, J C O'Keane, B F Dickey, J T LaMont, and C Pothoulakis

Section of Gastroenterology, Boston University School of Medicine, Massachusetts 02118.

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

Section of Gastroenterology, Boston University School of Medicine, Massachusetts 02118.

Find articles by Becker, S. in: PubMed | Google Scholar

Section of Gastroenterology, Boston University School of Medicine, Massachusetts 02118.

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

Section of Gastroenterology, Boston University School of Medicine, Massachusetts 02118.

Find articles by Joshi, M. in: PubMed | Google Scholar

Section of Gastroenterology, Boston University School of Medicine, Massachusetts 02118.

Find articles by O'Keane, J. in: PubMed | Google Scholar

Section of Gastroenterology, Boston University School of Medicine, Massachusetts 02118.

Find articles by Dickey, B. in: PubMed | Google Scholar

Section of Gastroenterology, Boston University School of Medicine, Massachusetts 02118.

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

Section of Gastroenterology, Boston University School of Medicine, Massachusetts 02118.

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

Published March 1, 1994 - More info

Published in Volume 93, Issue 3 on March 1, 1994
J Clin Invest. 1994;93(3):1257–1265. https://doi.org/10.1172/JCI117080.
© 1994 The American Society for Clinical Investigation
Published March 1, 1994 - Version history
View PDF
Abstract

Neutrophil infiltration is a prominent feature of Clostridium difficile-associated enteritis and colitis. The aim of this study was to examine the importance of neutrophil recruitment and neutrophil-mediated tissue damage in C. difficile toxin A-induced enteritis. Competitive binding experiments using purified 3H-toxin A demonstrated the presence of a single class of medium affinity receptors on rabbit neutrophils (Kd 7 x 10(-8) M). Pertussis toxin and the nonhydrolyzable GTP analog GTPgamma S both inhibited 3H-toxin A binding (by 56 and 65%, respectively), indicating that the rabbit neutrophil toxin A receptor is G protein linked. Toxin A elicited a dose-dependent (25-200 micrograms/ml) stimulation of neutrophil migration in vitro, and this functional effect was also pertussis toxin sensitive (69% inhibition). Treatment of neutrophils with R15.7, a blocking monoclonal antibody to the leuocyte adhesion molecule CD18, inhibited toxin A-stimulated neutrophil migration by 85% in vitro. Pretreatment of rabbits with R15.7 also prevented neutrophil infiltration of toxin A-exposed ileal loops in vivo as determined by histologic examination and by ileal tissue myeloperoxidase levels. Furthermore, R15.7 effected a substantial inhibition of fluid secretion (by 65%), mannitol permeability (by 66%), and histologic damage in toxin A-exposed ileal loops. Anti-CD18 (R15.7) had no inhibitory effect on cholera toxin enterotoxicity. These data demonstrate that C. difficile toxin A is a proinflammatory toxin whose enterotoxic effects are substantially dependent upon neutrophil recruitment.

Images.

Browse pages

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

Version history
  • Version 1 (March 1, 1994): No description
Advertisement
Advertisement