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. 1987 Oct;80(4):1104–1113. doi: 10.1172/JCI113167

Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers.

S Nash 1, J Stafford 1, J L Madara 1
PMCID: PMC442353  PMID: 3116044

Abstract

We describe a model to study the effects of polymorphonuclear leukocyte (PMN) transmigration on the intestinal epithelial barrier. Human PMN were induced to transmigrate across high resistance monolayers of a cultured human intestinal epithelial cell line (T84 cells) by chemotactic gradients produced by formyl methionyl leucyl phenylalanine (FMLP). With maximal transmigration monolayer resistance decreased by 48 +/- 12.6% in 15 min and by 83 +/- 1.6% in 60 min. This response was dependent on the size of the FMLP gradient and the density of PMN transmigration. The decrease in resistance correlated with number of PMN migrating across monolayers, and was accompanied by increases in flux of paracellular tracers. Macromolecular tracer studies localized the leak sites to foci at which PMN impaled the epithelium. Removal of the chemotactic gradient led to restoration of baseline resistance within 18 h. PMN transmigration across intestinal epithelial monolayers occurs via intercellular occluding junctions and may be associated with a reversible increase in epithelial permeability.

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Selected References

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  1. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cramer E. B., Milks L. C., Ojakian G. K. Transepithelial migration of human neutrophils: an in vitro model system. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4069–4073. doi: 10.1073/pnas.77.7.4069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dharmsathaphorn K., McRoberts J. A., Mandel K. G., Tisdale L. D., Masui H. A human colonic tumor cell line that maintains vectorial electrolyte transport. Am J Physiol. 1984 Feb;246(2 Pt 1):G204–G208. doi: 10.1152/ajpgi.1984.246.2.G204. [DOI] [PubMed] [Google Scholar]
  4. Evans C. W., Taylor J. E., Walker J. D., Simmons N. L. Transepithelial chemotaxis of rat peritoneal exudate cells. Br J Exp Pathol. 1983 Dec;64(6):644–654. [PMC free article] [PubMed] [Google Scholar]
  5. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  6. Hawker P. C., McKay J. S., Turnberg L. A. Electrolyte transport across colonic mucosa from patients with inflammatory bowel disease. Gastroenterology. 1980 Sep;79(3):508–511. [PubMed] [Google Scholar]
  7. Kumar N. B., Nostrant T. T., Appelman H. D. The histopathologic spectrum of acute self-limited colitis (acute infectious-type colitis). Am J Surg Pathol. 1982 Sep;6(6):523–529. doi: 10.1097/00000478-198209000-00004. [DOI] [PubMed] [Google Scholar]
  8. MARCHESI V. T. The site of leucocyte emigration during inflammation. Q J Exp Physiol Cogn Med Sci. 1961 Apr;46:115–118. doi: 10.1113/expphysiol.1961.sp001522. [DOI] [PubMed] [Google Scholar]
  9. Madara J. L., Dharmsathaphorn K. Occluding junction structure-function relationships in a cultured epithelial monolayer. J Cell Biol. 1985 Dec;101(6):2124–2133. doi: 10.1083/jcb.101.6.2124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Madara J. L., Stafford J., Dharmsathaphorn K., Carlson S. Structural analysis of a human intestinal epithelial cell line. Gastroenterology. 1987 May;92(5 Pt 1):1133–1145. doi: 10.1016/s0016-5085(87)91069-9. [DOI] [PubMed] [Google Scholar]
  11. Marasco W. A., Phan S. H., Krutzsch H., Showell H. J., Feltner D. E., Nairn R., Becker E. L., Ward P. A. Purification and identification of formyl-methionyl-leucyl-phenylalanine as the major peptide neutrophil chemotactic factor produced by Escherichia coli. J Biol Chem. 1984 May 10;259(9):5430–5439. [PubMed] [Google Scholar]
  12. Marcial M. A., Carlson S. L., Madara J. L. Partitioning of paracellular conductance along the ileal crypt-villus axis: a hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationships. J Membr Biol. 1984;80(1):59–70. doi: 10.1007/BF01868690. [DOI] [PubMed] [Google Scholar]
  13. Milks L. C., Brontoli M. J., Cramer E. B. Epithelial permeability and the transepithelial migration of human neutrophils. J Cell Biol. 1983 May;96(5):1241–1247. doi: 10.1083/jcb.96.5.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Milks L. C., Conyers G. P., Cramer E. B. The effect of neutrophil migration on epithelial permeability. J Cell Biol. 1986 Dec;103(6 Pt 2):2729–2738. doi: 10.1083/jcb.103.6.2729. [DOI] [PMC free article] [PubMed] [Google Scholar]

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