No conflicts of interest were declared.
Disruption of tight junctions during polymicrobial sepsis in vivo†
Article first published online: 20 JAN 2009
Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 218, Issue 2, pages 210–221, June 2009
How to Cite
Li, Q., Zhang, Q., Wang, C., Liu, X., Li, N. and Li, J. (2009), Disruption of tight junctions during polymicrobial sepsis in vivo. J. Pathol., 218: 210–221. doi: 10.1002/path.2525
- Issue published online: 5 MAY 2009
- Article first published online: 20 JAN 2009
- Accepted manuscript online: 20 JAN 2009 12:00AM EST
- Manuscript Accepted: 6 JAN 2009
- Manuscript Revised: 1 NOV 2008
- Manuscript Received: 16 AUG 2008
- National Basic Research Programme (973 Programme) in China. Grant Numbers: 2007CB513005, 2009CB522405
- National Natural Science Foundation in China. Grant Number: 30830098
- National Natural Science Foundation in China. Grant Number: 30672061
- Nanjing Military Command. Grant Number: 06Z40
- Military Scientific Research. Grant Number: 0603AM117
- tight junction;
- barrier function dysfunction;
- tight junction proteins
The disruption of intestinal epithelial tight junctions may result in barrier function dysfunction during polymicrobial sepsis. The pathophysiology of sepsis involves breakdown of barrier integrity, which correlates with adverse outcome during sepsis. However, the mechanisms underlying loss of barrier function in sepsis remain unknown. In the present study in mice, tight junction (TJ) structure was analysed by transmission electron microscopy; intestinal permeability was assessed using molecular tracer measurement; and the distribution of TJ proteins was investigated by immunofluorescence microscopy. The membrane microdomains of TJs were isolated using discontinuous sucrose density gradients and the expression of TJ proteins in these was determined by western blot. Immunofluorescence microscopy revealed that claudins 1, 3, 4, 5, and 8 were present predominantly in the microvillous surface of epithelial cells and along the lateral membranes of the cells; in sepsis, however, labelling of these proteins was present diffusely within cells and was no longer focused at the lateral cell boundaries. Moreover, the expression of claudin-2 was markedly up-regulated in sepsis. Using western blot analysis, we found that occludin and claudins were displaced from raft fractions to non-raft fractions in membrane microdomains of TJs in sepsis. In addition, the disruption of TJ structure was accompanied by increased intestinal permeability. Our results demonstrate for the first time that redistribution of TJ proteins in TJ membrane microdomains and redistribution of claudins in epithelial cells of the colon lead to alteration of TJ architecture and TJ barrier dysfunction during the development of polymicrobial sepsis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.