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. 1996 Nov;64(11):4480–4487. doi: 10.1128/iai.64.11.4480-4487.1996

Attachment of a noninvasive enteric pathogen, enteropathogenic Escherichia coli, to cultured human intestinal epithelial monolayers induces transmigration of neutrophils.

S D Savkovic 1, A Koutsouris 1, G Hecht 1
PMCID: PMC174401  PMID: 8890195

Abstract

An intense inflammatory cell infiltrate, consisting primarily of polymorphonuclear leukocytes (PMN), accompanies enteric infection by enteropathogenic Escherichia coli (EPEC). The mechanism(s) by which this pathogen elicits PMN recruitment has not been studied. To determine whether EPEC infection of intestinal epithelial cells induces PMN to transmigrate, an in vitro model consisting of cultured human intestinal epithelial monolayers (T84), a human EPEC strain (E2348/69), and isolated human PMN was used. Results of these studies showed that EPEC attachment to T84 monolayers stimulated the transepithelial migration of PMN in a dose-dependent fashion. This event was not attributable to the classic bacterial chemoattractants, n-formylated peptides, or other soluble bacterial factors. A nonadherent EPEC strain, JPN15, was unable to cause PMN to cross the epithelial monolayer. Epithelial protein synthesis was required for maximum EPEC-induced PMN transmigration to occur. Transfer assays demonstrated the presence of a chemokine in sterilized medium from infected monolayers. Neutralizing antibodies to interleukin 8 ablated approximately 50% of the chemotactic activity. Studies with EPEC mutant strains revealed that the eaeB gene, required for the activation of signal transduction pathways in host cells, was crucial for eliciting PMN transmigration. These data show for the first time that attachment of a noninvasive enteric pathogen to intestinal epithelial cells induces PMN transmigration. These findings strongly suggest that EPEC attachment to target host cells activates a signal transduction cascade which ultimately leads to the expression and release of an epithelium-derived chemotactic factor(s) for PMN.

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Selected References

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