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*Substance via MeSH
The Journal of Immunology, 1998, 161: 4301-4308.
Copyright © 1998 by The American Association of Immunologists

Effect of Cytotoxic Necrotizing Factor-1 on Actin Cytoskeleton in Human Monocytes: Role in the Regulation of Integrin-Dependent Phagocytosis

Christian Capo*, Sonia Meconi*, Muriel-Véronique Sanguedolce*, Nathalie Bardin{dagger}, Gilles Flatau{ddagger}, Patrice Boquet{ddagger} and Jean-Louis Mege1,*

* Unité des Rickettsies, Université de la Méditerranée, Centre National de la Recherche Scientifique, UPRESA 6020, Faculté de Médecine, and {dagger} Laboratoire d’Hématologie, Hôpital de la Conception, Marseille; and {ddagger} Institut National de la Santé et de la Recherche Médicale, Unité 452, Faculté de Médecine, Nice, France

Cytotoxic necrotizing factor-1 (CNF1) is isolated from pathogenic strains of Escherichia coli and catalyzes the activation of Rho GTPases by the deamidation of a glutamine residue. This toxin induces stress fiber formation, cell spreading, and membrane folding and promotes phagocytosis competence in epithelial cells. We show that CNF1 induces morphologic changes in monocytic cells: polarized-like shape in THP-1 cells, lamellipodia, and cell spreading in adherent monocytes. CNF1 also increased filamentous actin (F-actin) content in a time- and dose-dependent manner. In addition, the toxin profoundly reorganized the actin cytoskeleton: redistribution of F-actin in polarized deformations of THP-1 cells and disorganization of microfilament network in monocytes. We also studied the effects of CNF1 on phagocytosis. It markedly impaired the ingestion of unopsonized zymosan involving CR type 3. However, CNF1 had no effect on the uptake of iC3b-coated zymosan or IgG-mediated phagocytosis of SRBC. In addition, CNF1 induced clustering of CR3 and Fc{gamma}RII (CD32) but selectively impaired the colocalization of CR3 with F-actin. It is likely that CNF1-induced reorganization of actin cytoskeleton down-modulates integrin activation-dependent phagocytosis by preventing the codistribution of CR3 with F-actin. CNF1 may control some features of integrin-dependent phagocytosis in myeloid cells through its action on Rho GTP binding proteins and cytoskeletal organization.




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