Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 Oct;63(10):4054–4062. doi: 10.1128/iai.63.10.4054-4062.1995

Escherichia coli induces transuroepithelial neutrophil migration by an intercellular adhesion molecule-1-dependent mechanism.

W W Agace 1, M Patarroyo 1, M Svensson 1, E Carlemalm 1, C Svanborg 1
PMCID: PMC173570  PMID: 7558319

Abstract

During bacterial infections at mucosal sites, neutrophils migrate to the mucosa and cross the epithelial barrier. We have examined neutrophil migration across Escherichia coli-stimulated uroepithelial cell layers in an attempt to more fully understand this process. Stimulation of uroepithelial cells with E. coli or interleukin-1 alpha (IL-1 alpha) induced transepithelial neutrophil migration in a time- and stimulant dose-dependent manner. Uroepithelial cell lines and nontransformed uroepithelial cells expressed intercellular adhesion molecule-1 (ICAM-1) but not ICAM-2, E-selectin, or P-selectin. Epithelial ICAM-1 expression was enhanced after stimulation with E. coli or IL-1 alpha. Anti-ICAM-1 antibody reduced transepithelial neutrophil migration by 61 to 85%, indicating that neutrophils bound ICAM-1 on the epithelial surface. Antibodies to CD18 and CD11b reduced migration by 70 to 79%, suggesting that CD11b/CD18 (Mac-1) was acting as the neutrophil receptor for ICAM-1 in this process. Anti-CD11a antibodies had no effect on neutrophil migration. In conclusion, E. coli induced ICAM-1- and Mac-1-dependent transepithelial neutrophil migration. Previous studies have shown that urinary tract epithelial cells secrete IL-8 when exposed to E. coli or IL-1 alpha. These observations suggest that epithelial cells play an active role in neutrophil migration during urinary tract infections.

Full Text

The Full Text of this article is available as a PDF (674.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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., 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]
  3. Andersson P., Engberg I., Lidin-Janson G., Lincoln K., Hull R., Hull S., Svanborg C. Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence. Infect Immun. 1991 Sep;59(9):2915–2921. doi: 10.1128/iai.59.9.2915-2921.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bevilacqua M. P., Nelson R. M. Selectins. J Clin Invest. 1993 Feb;91(2):379–387. doi: 10.1172/JCI116210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  6. Colgan S. P., Parkos C. A., Delp C., Arnaout M. A., Madara J. L. Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-gamma in a highly polarized fashion. J Cell Biol. 1993 Feb;120(3):785–798. doi: 10.1083/jcb.120.3.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Diamond M. S., Staunton D. E., de Fougerolles A. R., Stacker S. A., Garcia-Aguilar J., Hibbs M. L., Springer T. A. ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). J Cell Biol. 1990 Dec;111(6 Pt 2):3129–3139. doi: 10.1083/jcb.111.6.3129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dohlsten M., Hedlund G., Lando P. A., Trowsdale J., Altmann D., Patarroyo M., Fischer H., Kalland T. Role of the adhesion molecule ICAM-1 (CD54) in staphylococcal enterotoxin-mediated cytotoxicity. Eur J Immunol. 1991 Jan;21(1):131–135. doi: 10.1002/eji.1830210120. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Elgavish A. Effects of Escherichia coli and E. coli lipopolysaccharides on the function of human ureteral epithelial cells cultured in serum-free medium. Infect Immun. 1993 Aug;61(8):3304–3312. doi: 10.1128/iai.61.8.3304-3312.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hedges S., Agace W., Svensson M., Sjögren A. C., Ceska M., Svanborg C. Uroepithelial cells are part of a mucosal cytokine network. Infect Immun. 1994 Jun;62(6):2315–2321. doi: 10.1128/iai.62.6.2315-2321.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hedges S., Agace W., Svensson M., Svanborg C. Cyclosporin A does not inhibit IL-1 alpha-induced epithelial cell IL-6 secretion. Scand J Immunol. 1993 May;37(5):581–586. doi: 10.1111/j.1365-3083.1993.tb02575.x. [DOI] [PubMed] [Google Scholar]
  13. Hedges S., Anderson P., Lidin-Janson G., de Man P., Svanborg C. Interleukin-6 response to deliberate colonization of the human urinary tract with gram-negative bacteria. Infect Immun. 1991 Jan;59(1):421–427. doi: 10.1128/iai.59.1.421-427.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Ishikura H., Takahashi C., Kanagawa K., Hirata H., Imai K., Yoshiki T. Cytokine regulation of ICAM-1 expression on human renal tubular epithelial cells in vitro. Transplantation. 1991 Jun;51(6):1272–1275. doi: 10.1097/00007890-199106000-00024. [DOI] [PubMed] [Google Scholar]
  16. Lawrence M. B., Springer T. A. Neutrophils roll on E-selectin. J Immunol. 1993 Dec 1;151(11):6338–6346. [PubMed] [Google Scholar]
  17. Linder H., Engberg I., van Kooten C., de Man P., Svanborg-Edén C. Effects of anti-inflammatory agents on mucosal inflammation induced by infection with gram-negative bacteria. Infect Immun. 1990 Jul;58(7):2056–2060. doi: 10.1128/iai.58.7.2056-2060.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Luscinskas F. W., Cybulsky M. I., Kiely J. M., Peckins C. S., Davis V. M., Gimbrone M. A., Jr Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1. J Immunol. 1991 Mar 1;146(5):1617–1625. [PubMed] [Google Scholar]
  19. Marlin S. D., Springer T. A. Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell. 1987 Dec 4;51(5):813–819. doi: 10.1016/0092-8674(87)90104-8. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Miller T. E., Findon G., Cawley S. Cellular basis of host defence in pyelonephritis. III. Deletion of individual components. Br J Exp Pathol. 1987 Jun;68(3):377–388. [PMC free article] [PubMed] [Google Scholar]
  22. Nash S., Stafford J., Madara J. L. Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers. J Clin Invest. 1987 Oct;80(4):1104–1113. doi: 10.1172/JCI113167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nortamo P., Li R., Renkonen R., Timonen T., Prieto J., Patarroyo M., Gahmberg C. G. The expression of human intercellular adhesion molecule-2 is refractory to inflammatory cytokines. Eur J Immunol. 1991 Oct;21(10):2629–2632. doi: 10.1002/eji.1830211049. [DOI] [PubMed] [Google Scholar]
  24. Parkos C. A., Delp C., Arnaout M. A., Madara J. L. Neutrophil migration across a cultured intestinal epithelium. Dependence on a CD11b/CD18-mediated event and enhanced efficiency in physiological direction. J Clin Invest. 1991 Nov;88(5):1605–1612. doi: 10.1172/JCI115473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Patarroyo M., Clark E. A., Prieto J., Kantor C., Gahmberg C. G. Identification of a novel adhesion molecule in human leukocytes by monoclonal antibody LB-2. FEBS Lett. 1987 Jan 5;210(2):127–131. doi: 10.1016/0014-5793(87)81321-2. [DOI] [PubMed] [Google Scholar]
  26. Pober J. S., Bevilacqua M. P., Mendrick D. L., Lapierre L. A., Fiers W., Gimbrone M. A., Jr Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol. 1986 Mar 1;136(5):1680–1687. [PubMed] [Google Scholar]
  27. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  28. Prieto J., Takei F., Gendelman R., Christenson B., Biberfeld P., Patarroyo M. MALA-2, mouse homologue of human adhesion molecule ICAM-1 (CD54). Eur J Immunol. 1989 Sep;19(9):1551–1557. doi: 10.1002/eji.1830190906. [DOI] [PubMed] [Google Scholar]
  29. Salcedo R., Patarroyo M. Constitutive alpha V beta 3 integrin-mediated adhesion of human lymphoid B cells to vitronectin substrate. Cell Immunol. 1995 Feb;160(2):165–172. doi: 10.1016/0008-8749(95)80023-c. [DOI] [PubMed] [Google Scholar]
  30. Shahin R. D., Engberg I., Hagberg L., Svanborg Edén C. Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection. J Immunol. 1987 May 15;138(10):3475–3480. [PubMed] [Google Scholar]
  31. Somersalo K., Tarkkanen J., Patarroyo M., Saksela E. Involvement of beta 2-integrins in the migration of human natural killer cells. J Immunol. 1992 Jul 15;149(2):590–598. [PubMed] [Google Scholar]
  32. Svensson M., Lindstedt R., Radin N. S., Svanborg C. Epithelial glucosphingolipid expression as a determinant of bacterial adherence and cytokine production. Infect Immun. 1994 Oct;62(10):4404–4410. doi: 10.1128/iai.62.10.4404-4410.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weiland J. E., Davis W. B., Holter J. F., Mohammed J. R., Dorinsky P. M., Gadek J. E. Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis. 1986 Feb;133(2):218–225. doi: 10.1164/arrd.1986.133.2.218. [DOI] [PubMed] [Google Scholar]
  34. Yardley J. H., Donowitz M. Colo-rectal biopsy in inflammatory bowel disease. Monogr Pathol. 1977;(18):50–94. [PubMed] [Google Scholar]
  35. de Fougerolles A. R., Stacker S. A., Schwarting R., Springer T. A. Characterization of ICAM-2 and evidence for a third counter-receptor for LFA-1. J Exp Med. 1991 Jul 1;174(1):253–267. doi: 10.1084/jem.174.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES