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. 1997 Aug;65(8):3451–3456. doi: 10.1128/iai.65.8.3451-3456.1997

Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration.

G Godaly 1, A E Proudfoot 1, R E Offord 1, C Svanborg 1, W W Agace 1
PMCID: PMC175488  PMID: 9234811

Abstract

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.

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Selected References

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  1. Agace W. W., Hedges S. R., Ceska M., Svanborg C. Interleukin-8 and the neutrophil response to mucosal gram-negative infection. J Clin Invest. 1993 Aug;92(2):780–785. doi: 10.1172/JCI116650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agace W. W., Patarroyo M., Svensson M., Carlemalm E., Svanborg C. Escherichia coli induces transuroepithelial neutrophil migration by an intercellular adhesion molecule-1-dependent mechanism. Infect Immun. 1995 Oct;63(10):4054–4062. doi: 10.1128/iai.63.10.4054-4062.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agace W., Hedges S., Andersson U., Andersson J., Ceska M., Svanborg C. Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect Immun. 1993 Feb;61(2):602–609. doi: 10.1128/iai.61.2.602-609.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Alouani S., Gaertner H. F., Mermod J. J., Power C. A., Bacon K. B., Wells T. N., Proudfoot A. E. A fluorescent interleukin-8 receptor probe produced by targetted labelling at the amino terminus. Eur J Biochem. 1995 Jan 15;227(1-2):328–334. doi: 10.1111/j.1432-1033.1995.tb20393.x. [DOI] [PubMed] [Google Scholar]
  5. Baggiolini M., Dewald B., Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179. [PubMed] [Google Scholar]
  6. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chuntharapai A., Lee J., Burnier J., Wood W. I., Hébert C., Kim K. J. Neutralizing monoclonal antibodies to human IL-8 receptor A map to the NH2-terminal region of the receptor. J Immunol. 1994 Feb 15;152(4):1783–1789. [PubMed] [Google Scholar]
  8. Chuntharapai A., Lee J., Hébert C. A., Kim K. J. Monoclonal antibodies detect different distribution patterns of IL-8 receptor A and IL-8 receptor B on human peripheral blood leukocytes. J Immunol. 1994 Dec 15;153(12):5682–5688. [PubMed] [Google Scholar]
  9. Cooper D., Lindberg F. P., Gamble J. R., Brown E. J., Vadas M. A. Transendothelial migration of neutrophils involves integrin-associated protein (CD47). Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3978–3982. doi: 10.1073/pnas.92.9.3978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crabtree J. E., Peichl P., Wyatt J. I., Stachl U., Lindley I. J. Gastric interleukin-8 and IgA IL-8 autoantibodies in Helicobacter pylori infection. Scand J Immunol. 1993 Jan;37(1):65–70. doi: 10.1111/j.1365-3083.1993.tb01666.x. [DOI] [PubMed] [Google Scholar]
  11. Crabtree J. E., Wyatt J. I., Trejdosiewicz L. K., Peichl P., Nichols P. H., Ramsay N., Primrose J. N., Lindley I. J. Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa. J Clin Pathol. 1994 Jan;47(1):61–66. doi: 10.1136/jcp.47.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eckmann L., Kagnoff M. F., Fierer J. Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry. Infect Immun. 1993 Nov;61(11):4569–4574. doi: 10.1128/iai.61.11.4569-4574.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Edén C. S., Freter R., Hagberg L., Hull R., Hull S., Leffler H., Schoolnik G. Inhibition of experimental ascending urinary tract infection by an epithelial cell-surface receptor analogue. Nature. 1982 Aug 5;298(5874):560–562. doi: 10.1038/298560a0. [DOI] [PubMed] [Google Scholar]
  14. Hedges S. R., Agace W. W., Svanborg C. Epithelial cytokine responses and mucosal cytokine networks. Trends Microbiol. 1995 Jul;3(7):266–270. doi: 10.1016/s0966-842x(00)88941-6. [DOI] [PubMed] [Google Scholar]
  15. Hedges S., Svensson M., Svanborg C. Interleukin-6 response of epithelial cell lines to bacterial stimulation in vitro. Infect Immun. 1992 Apr;60(4):1295–1301. doi: 10.1128/iai.60.4.1295-1301.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Holmes W. E., Lee J., Kuang W. J., Rice G. C., Wood W. I. Structure and functional expression of a human interleukin-8 receptor. Science. 1991 Sep 13;253(5025):1278–1280. doi: 10.1126/science.1840701. [DOI] [PubMed] [Google Scholar]
  17. Huang J., O'Toole P. W., Doig P., Trust T. J. Stimulation of interleukin-8 production in epithelial cell lines by Helicobacter pylori. Infect Immun. 1995 May;63(5):1732–1738. doi: 10.1128/iai.63.5.1732-1738.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Huber A. R., Kunkel S. L., Todd R. F., 3rd, Weiss S. J. Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science. 1991 Oct 4;254(5028):99–102. doi: 10.1126/science.1718038. [DOI] [PubMed] [Google Scholar]
  19. Jung H. C., Eckmann L., Yang S. K., Panja A., Fierer J., Morzycka-Wroblewska E., Kagnoff M. F. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest. 1995 Jan;95(1):55–65. doi: 10.1172/JCI117676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ko Y. C., Mukaida N., Ishiyama S., Tokue A., Kawai T., Matsushima K., Kasahara T. Elevated interleukin-8 levels in the urine of patients with urinary tract infections. Infect Immun. 1993 Apr;61(4):1307–1314. doi: 10.1128/iai.61.4.1307-1314.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee J., Horuk R., Rice G. C., Bennett G. L., Camerato T., Wood W. I. Characterization of two high affinity human interleukin-8 receptors. J Biol Chem. 1992 Aug 15;267(23):16283–16287. [PubMed] [Google Scholar]
  22. Loike J. D., el Khoury J., Cao L., Richards C. P., Rascoff H., Mandeville J. T., Maxfield F. R., Silverstein S. C. Fibrin regulates neutrophil migration in response to interleukin 8, leukotriene B4, tumor necrosis factor, and formyl-methionyl-leucyl-phenylalanine. J Exp Med. 1995 May 1;181(5):1763–1772. doi: 10.1084/jem.181.5.1763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Massion P. P., Inoue H., Richman-Eisenstat J., Grunberger D., Jorens P. G., Housset B., Pittet J. F., Wiener-Kronish J. P., Nadel J. A. Novel Pseudomonas product stimulates interleukin-8 production in airway epithelial cells in vitro. J Clin Invest. 1994 Jan;93(1):26–32. doi: 10.1172/JCI116954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McCormick B. A., Colgan S. P., Delp-Archer C., Miller S. I., Madara J. L. Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. J Cell Biol. 1993 Nov;123(4):895–907. doi: 10.1083/jcb.123.4.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McCormick B. A., Hofman P. M., Kim J., Carnes D. K., Miller S. I., Madara J. L. Surface attachment of Salmonella typhimurium to intestinal epithelia imprints the subepithelial matrix with gradients chemotactic for neutrophils. J Cell Biol. 1995 Dec;131(6 Pt 1):1599–1608. doi: 10.1083/jcb.131.6.1599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Moser B., Schumacher C., von Tscharner V., Clark-Lewis I., Baggiolini M. Neutrophil-activating peptide 2 and gro/melanoma growth-stimulatory activity interact with neutrophil-activating peptide 1/interleukin 8 receptors on human neutrophils. J Biol Chem. 1991 Jun 5;266(16):10666–10671. [PubMed] [Google Scholar]
  27. Murphy P. M., Tiffany H. L. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science. 1991 Sep 13;253(5025):1280–1283. doi: 10.1126/science.1891716. [DOI] [PubMed] [Google Scholar]
  28. Oishi K., Sonoda F., Kobayashi S., Iwagaki A., Nagatake T., Matsushima K., Matsumoto K. Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases. Infect Immun. 1994 Oct;62(10):4145–4152. doi: 10.1128/iai.62.10.4145-4152.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Parkos C. A., Colgan S. P., Liang T. W., Nusrat A., Bacarra A. E., Carnes D. K., Madara J. L. CD47 mediates post-adhesive events required for neutrophil migration across polarized intestinal epithelia. J Cell Biol. 1996 Feb;132(3):437–450. doi: 10.1083/jcb.132.3.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Raqib R., Lindberg A. A., Wretlind B., Bardhan P. K., Andersson U., Andersson J. Persistence of local cytokine production in shigellosis in acute and convalescent stages. Infect Immun. 1995 Jan;63(1):289–296. doi: 10.1128/iai.63.1.289-296.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Richman-Eisenstat J. B., Jorens P. G., Hébert C. A., Ueki I., Nadel J. A. Interleukin-8: an important chemoattractant in sputum of patients with chronic inflammatory airway diseases. Am J Physiol. 1993 Apr;264(4 Pt 1):L413–L418. doi: 10.1152/ajplung.1993.264.4.L413. [DOI] [PubMed] [Google Scholar]
  32. Rot A. Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration. Immunol Today. 1992 Aug;13(8):291–294. doi: 10.1016/0167-5699(92)90039-A. [DOI] [PubMed] [Google Scholar]
  33. Sharma S. A., Tummuru M. K., Miller G. G., Blaser M. J. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect Immun. 1995 May;63(5):1681–1687. doi: 10.1128/iai.63.5.1681-1687.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tanaka Y., Adams D. H., Shaw S. Proteoglycans on endothelial cells present adhesion-inducing cytokines to leukocytes. Immunol Today. 1993 Mar;14(3):111–115. doi: 10.1016/0167-5699(93)90209-4. [DOI] [PubMed] [Google Scholar]
  35. Walz A., Zwahlen R., Baggiolini M. Formation and biological properties of neutrophil activating peptide 2 (NAP-2). Adv Exp Med Biol. 1991;305:39–46. doi: 10.1007/978-1-4684-6009-4_5. [DOI] [PubMed] [Google Scholar]
  36. Webb L. M., Ehrengruber M. U., Clark-Lewis I., Baggiolini M., Rot A. Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7158–7162. doi: 10.1073/pnas.90.15.7158. [DOI] [PMC free article] [PubMed] [Google Scholar]

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