PMID- 11037974 OWN - NLM STAT- MEDLINE DCOM- 20001103 LR - 20051117 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 68 IP - 4 DP - 2000 Oct TI - 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. PG - 522-8 AB - 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. FAU - Hofman, P AU - Hofman P AD - Laboratoire d'Anatomie-Pathologique, INSERM U364, Nice, France. hofman@unice.fr FAU - Le Negrate, G AU - Le Negrate G FAU - Mograbi, B AU - Mograbi B FAU - Hofman, V AU - Hofman V FAU - Brest, P AU - Brest P FAU - Alliana-Schmid, A AU - Alliana-Schmid A FAU - Flatau, G AU - Flatau G FAU - Boquet, P AU - Boquet P FAU - Rossi, B AU - Rossi B LA - eng PT - Journal Article PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Actins) RN - 0 (Bacterial Toxins) RN - 0 (Cytotoxins) RN - 0 (Escherichia coli Proteins) RN - 0 (Macrophage-1 Antigen) RN - 0 (Opsonin Proteins) RN - 0 (Reactive Oxygen Species) RN - 106803-33-2 (cytotoxic necrotizing factor type 1) RN - 11062-77-4 (Superoxides) RN - 9010-72-4 (Zymosan) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) SB - IM MH - Actins/metabolism MH - Bacterial Toxins/*pharmacology MH - Cell Adhesion/drug effects MH - Cells, Cultured MH - Cytoskeleton/drug effects MH - Cytotoxins/*pharmacology MH - Epithelial Cells/cytology MH - Escherichia coli/*pathogenicity MH - *Escherichia coli Proteins MH - Humans MH - Inflammation/chemically induced MH - Intestinal Mucosa/cytology MH - Macrophage-1 Antigen/metabolism MH - Neutrophils/*drug effects/microbiology/physiology/ultrastructure MH - Opsonin Proteins/pharmacology MH - Phagocytosis/*drug effects MH - Reactive Oxygen Species/metabolism MH - Respiratory Burst/*drug effects MH - Superoxides/metabolism MH - Virulence MH - Zymosan/pharmacology MH - rho GTP-Binding Proteins/antagonists & inhibitors/physiology EDAT- 2000/10/19 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/19 11:00 PHST- 2000/10/19 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/19 11:00 [entrez] PST - ppublish SO - J Leukoc Biol. 2000 Oct;68(4):522-8.