ESCHERICHIA-COLI CYTOTOXIC NECROTIZING FACTOR-1 EFFACES MICROVILLI AND DECREASES TRANSMIGRATION OF POLYMORPHONUCLEAR LEUKOCYTES IN INTESTINAL T84 EPITHELIAL-CELL MONOLAYERS

Cytotoxic necrotizing factor type 1 (CNF1), a 110-kDa toxin-like prote in from pathogenic Escherichia coli strains, induces an actin cytoskel eton reorganization consisting of the formation of prominent stress fi bers by permanent activation of the small GTP-binding protein Rho. Sin ce p21Rho regulates tight-junction permeability and periljunctional ac tin reorganization in epithelial intestinal cells (A. Nusrat, M. Giry, J. R. Turner, S. P. Colgan, C. A. Parkos, E. Lemichez, P. Boquet, and J. L. Madara, Proc. Natl. Acad. Sci. USA 92:10629-10633, 1995), we us ed polarized T84 epithelial intestinal cell monolayers to examine,whet her CNF1 could affect microvillus structure, transepithelial resistanc e, and polymorphonuclear leukocyte (PMN) transmigration. Incubation of T84 cells with CNF1 did not influence transepithelial resistance, sug gesting that barrier function and surface polarity were not affected b y the toxin. However, CNF1 effaced intestinal cell microvilli and indu ced a strong decrease of PMN transepithelial migration in either the l uminal-to-basolateral or the basolateral-to-luminal direction. CNF1 co uld thus be a virulence factor exhibiting a new type of combined activ ity consisting of effacing of microvilli and occlusion of the epitheli al barrier to PMNs. Attenuated transepithelial migration of PMNs could result in the enhanced growth and protection of luminal bacteria.