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(Journal of Leukocyte Biology. 2000;68:522-528.)
© 2000 by Society for Leukocyte Biology

Escherichia coli cytotoxic necrotizing factor-1 (CNF-1) increases the adherence to epithelia and the oxidative burst of human polymorphonuclear leukocytes but decreases bacteria phagocytosis

Paul Hofman*,{dagger}, Gaëlle Le Negrate{dagger}, Baharia Mograbi{dagger}, Véronique Hofman*, Patrick Brest{dagger}, Annie Alliana-Schmid{dagger}, Gilles Flatau{ddagger}, Patrice Boquet{ddagger} and Bernard Rossi{dagger}

* Laboratoire d’Anatomie-Pathologique,
{dagger} INSERM U364, and
{ddagger} INSERM U452, IFR 50, Faculté de Médecine, Nice, France

Correspondence: Paul Hofman, M.D., Ph.D., INSERM unité 364, IFR 50, Faculté de Médecine, avenue de Valombrose, 06107 Nice, Cédex 02, France. E-mail: hofman{at}unice.fr

Recruitment of polymorphonuclear leukocytes (PMNL) is a hallmark of both urinary and digestive infections caused by Escherichia coli. Cytotoxic necrotizing factor 1 (CNF-1) is a toxin produced by uropathogenic E. coli strains that mediates its effects via the activation of small GTP-binding proteins. However, the role and the consequences of CNF-1 on PMNL physiology remain largely unknown. In this study, we provide evidence that CNF-1 dramatically affects the PMNL cytoskeleton architecture by inducing an increased content of F-actin. Furthermore, we demonstrate that CNF-1 increases functional features of PMNL, such as superoxide generation and adherence on epithelial T84 monolayers, but significantly decreases their phagocytic function. Our results suggest that CNF-1 may behave as a virulence factor in urinary or digestive infection by stimulating PMNL cytotoxicity as a result of its enhancing effect on their adherence to epithelial cells as well as the production of radical oxygen products. Moreover, the decreased phagocytosis of PMNL induced by CNF-1 likely facilitates growth of bacteria. In these conditions, CNF-1 would intervene in the initiation and in the perpetuation of the inflammatory process.

Key Words: CNF-1 • polymorphonuclear leukocytes • cytoskeleton • Rho • Rac • Cdc42 • small GTPases • integrins




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