Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration.
Escherichia coli stimulates neutrophil migration across human uroepithelial cell layers. This study investigated the role of the neutrophil chemokine interleukin-8 (IL-8) in this process. E. coli and IL-1alpha stimulated urinary tract epithelial layers to secrete IL-8 and induced transepithelial neutrophil migration. Anti-IL-8 antibody reduced neutrophil migration across epithelial cell layers, indicating a central role for this chemokine in the migration process. Furthermore, addition of recombinant IL-8 to unstimulated cell layers was sufficient to induce migration. The IL-8 dependence of neutrophil migration was maintained after removal of soluble IL-8 by washing of the cell layers. Flow cytometry analysis with fluorescein isothiocyanate-labelled IL-8 confirmed IL-8's ability to bind to the epithelial cell surface. Indirect immunofluorescence with confocal laser scanning microscopy showed that IL-8 associated with the epithelial cell layers. Prior incubation of neutrophils with antibodies to IL-8 receptor A (IL-8RA) reduced neutrophil migration. Anti-IL-8 RB antibody had no effect on neutrophil migration. These results demonstrate that IL-8 plays a key role in E. coli- or IL-1alpha-induced transuroepithelial migration and suggest that epithelial cell-produced IL-8 interacts with IL-8RA on the neutrophil surface.
Godaly
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G
Department of Medical Microbiology, Lund University, Sweden. gabriela.godaly@mmb.lu.se
Proudfoot
A E
AE
Offord
R E
RE
Svanborg
C
C
Agace
W W
WW
D015703:Antigens, CD / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells; D004926:Escherichia coli / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology*; D023062:Receptors, Interleukin-8A; D014551:Urinary Tract / Q000166:cytology*
D015703:Antigens, CD; D007375:Interleukin-1; D016209:Interleukin-8; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A